rs201212113

Variant names:

• chr19-50409147-A-C
• NM_002691.4:c.1918A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-50409147-A-C
• chr19-50409147-A-G

Variant summary

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

The NM_002691.4(POLD1):​c.1918A>C​(p.Thr640Pro) 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. T640A) 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: 6.43

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 rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.1918A>C	p.Thr640Pro	missense_variant	Exon 16 of 27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.1918A>C	p.Thr640Pro	missense_variant	Exon 16 of 27	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	2.9	M;.;.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.0	D;.;.;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.90	P;.;.;P
Vest4		0.54
MutPred		0.58		Gain of catalytic residue at T640 (P = 0.001);.;.;Gain of catalytic residue at T640 (P = 0.001);
MVP		0.73
MPC		1.8
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.93
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-50912404;