Table 2.
Genes and variants reported in autosomal recessive familial MD
| Gene | Chr | Positiona | ID | cDNA | Protein | Variant effect | Allelic frequencyb | ACMG classification | CADD score | |
|---|---|---|---|---|---|---|---|---|---|---|
| gnomAD | Other | |||||||||
| STRC | 15 | 43604750 | rs144948296 | NM_153700.2:c.4027C >T | p.Gln1343* | Nonsense | 1.97 × 10–5 | NF (CSVS) | Pathogenic | 40.00 |
| 3.43 × 10–4 (ExAC) | (PSV1, PS4, PM2, PP3, PP5) | |||||||||
| HMX2 | 10 | 123150118 | rs1274867386 | NM_005519.2:c.817 T >A | p.Tyr273Asn | Missensed | 6.57 × 10–6 | NF (CSVS) | Likely pathogenic | 31.00 |
| (PS4, PM2, PP3) | ||||||||||
| TMEM55 | 14 | 20459211 | rs201529818 | NM_001100814.3:c.706C >T | p.Leu229Phe | Missensed | 9.56 × 10–4 | NF (CSVS) | Uncertain significance | 25.80 |
| (PIP4P1) | 8.2 × 10–5 (ExAC) | (PS4, PP3, BS1) | ||||||||
| OTOG | 11 | 17553211 | rs552304627 | NM_001292063.2:c.421G >A | p.Val141Met | Missensed | 8.35 × 10–4 | 4.1 × 10–4 (ExAC) | Pathogenic | 33.00 |
| 4 × 10–3 (CSVS) | (PVS1, PS4, PM2, PP3, BP1) | |||||||||
| 11 | 17557227 | rs61978648 | NM_001292063.2:c.805G >A | p.Val269Ile | Missensec, d | 2.04 × 10–2 | 1.4 × 10–2 (CSVS) | Likely benign | 19.12 | |
| 8.01 × 10–3 (ExAC) | (PS4, BP1, BP4, BP6) | |||||||||
| 11 | 17573200 | - | NM_001292063.2:c.2203C >A | p.Pro747Thr | Missense | Novel | Uncertain significance | 21.90 | ||
| (PS4, PM2, BP1, BP4) | ||||||||||
| 11 | 17599671 | rs117005078 | NM_001292063.2:c.3719C >T | p.Pro1240Leu | Missensed | 3.3 × 10–3 | 4 × 10–3 (CSVS) | Likely pathogenic | 33.00 | |
| 1.68 × 10–3 (ExAC) | (PS4, PM2, PP3, BP1) | |||||||||
| 11 | 17606001 | rs145689709 | NM_001292063.2:c.4058G >A | p.Arg1353Gln | Missensec, d | 2.84 × 10–3 | 6 × 10–3 (CSVS) | Uncertain significance | 22.00 | |
| 1.98 × 10–3 (ExAC) | (PS4, PM2, BP1, BP4, BP6) | |||||||||
| 11 | 17609906 | rs117380920 | NM_001292063.2:c.4642C >T | p.Leu1548Phe | Missensec | 8 × 10–3 | 1.3 × 10–2 (CSVS) | Benign | 12.42 | |
| 1.07 × 10–2 (ExAC) | (PS4, BS1, BS2, BP1, BP4, BP6) | |||||||||
| 11 | 17611374 | rs61736002 | NM_001292063.2:c.6110C >T | p.Ala2037Val | Missensed | 2.41 × 10–3 | 4 × 10–3 (CSVS) | Uncertain significance | 7.61 | |
| 3.74 × 10–3 (ExAC) | (PS4, PM2, BP1, BP4) | |||||||||
| 11 | 17635125 | rs76461792 | NM_001292063.2:c.7667G >A | p.Arg2556Gln | Missensed | 3.06 × 10–3 | 4 × 10–3 (CSVS) | Benign | 23.50 | |
| 2.95 × 10–3 (ExAC) | (PS4, BS1, BS2, BP1, BP4, BP6) | |||||||||
| 11 | 17642200 | rs117315845 | NM_001292063.2:c.8405G >A | p.Arg2802His | Missensec, d | 2.04 × 10–3 | 6 × 10–3 (CSVS) | Uncertain significance | 16.79 | |
| 3.68 × 10–3 (ExAC) | (PS4, PM2, BP1, BP4, BP6) | |||||||||
| 11 | 17645592 | rs61997203 | NM_001292063.2:c.8526G >C | p.Lys2842Asn | Missense | 1.57 × 10–2 | 1.9 × 10–2 (CSVS) | Benign | 24.20 | |
| 9.79 × 10–3 (ExAC) | (PS4, BS1, BS2, BP1, BP6) | |||||||||
| LSAMP | 3 | 115842555 | - | NM_001318915.2:c.673 T >C | p. Lys225Glu | Missense | Novel | Likely pathogenic | 25.90 | |
| (PS4, PM2) | ||||||||||
ACMG American College of Medical Genetics and Genomics, AR autosomal recessive inheritance pattern, CADD Combined Annotation Dependent Depletion, CSVS Collaborative Spanish Variant Server, ExAC Exome Aggregation Consortium, gnomAD Genome Aggregation Database, ID reference Single Nucleotide Polymorphism identifier, NF not found
*stop codon
aPositions have been updated according to the GRCh38/hg38 reference genome
ballelic frequencies reported in the original reports have been updated according to the available information in the last version of the reference database (gnomAD v3.1.2)
cincomplete penetrance
dmultiple inheritance