rs753797045

Positions:

• chr19-50413440-C-A
• chr19-50413440-C-T

Variant summary

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

The NM_002691.4(POLD1):​c.2169C>A​(p.Phe723Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

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]

POLD1 (HGNC:):

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	Protein	UniProt
POLD1	NM_002691.4	c.2169C>A	p.Phe723Leu	missense_variant	18/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.2169C>A	p.Phe723Leu	missense_variant	18/27	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.62	D
LIST_S2	Pathogenic	0.97	.;.;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.0	D;.;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		0.41	B;.;.;B
Vest4		0.56
MutPred		0.55		Gain of MoRF binding (P = 0.121);.;.;Gain of MoRF binding (P = 0.121);
MVP		0.45
MPC		1.7
ClinPred		0.99	D
GERP RS		-2.5
Varity_R		0.89
gMVP		0.89

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: chr19-50916697;