Table 2.

POLD1 germline variants in the exonuclease domain identified by next‐generation sequencing

Patient	Alteration in genomic DNA	Protein alteration	MAF	rsID	Mutation taster	SIFT	PolyPhen−2	Grantham distance	Align GVGD	Segregation	CADD	Variant classification
P1, P2	c.961G>A	p.Gly321Ser	ExAC=0.0005 Go‐ESP=0.0002 TOPMED=0.0003	Rs41554817	Disease causing	Deleterious	Possibly damaging	Predicted not to be deleterious	Likely to interfere with function	P1: Segregation not performed, unclear family history For P2: not segregate in tested family members	Predicted to be pathogenic	VUS
P3	c.955 T>G	p.Cys319Gly	N.A	N.A	Disease causing	Deleterious	Probably damaging	Predicted to be deleterious	Highly likely to interfere with function	Not segregate in tested family members	Predicted to be pathogenic	VUS

MAF: minor allele frequency; rsID: variant identifier in dbSNP, ExAc: exome aggregation consortium; Go‐ESP: exome sequencing project; TOPMED: trans‐omics in precision medicine; N3009.A: not available; CADD: Combined Annotation Dependent; VUS: variant of uncertain significance.

GenBank reference sequence: POLD1; NM_002691.3