19-50408792-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002691.4(POLD1):c.1783G>T(p.Asp595Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D595N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.69

Genes affected

POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLD1	NM_002691.4	c.1783G>T	p.Asp595Tyr	missense_variant	15/27	ENST00000440232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD1	ENST00000440232.7	c.1783G>T	p.Asp595Tyr	missense_variant	15/27	1	NM_002691.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.6	H;.;.;H
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Benign	0.076	T;D;D;T
Polyphen		0.98	D;.;.;D
Vest4		0.63
MutPred		0.67		Gain of methylation at K591 (P = 0.0446);.;.;Gain of methylation at K591 (P = 0.0446);
MVP		0.57
MPC		1.8
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.64
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50912049;