rs368940099

chr19-50402280-C-Achr19-50402280-C-Gchr19-50402280-C-T

Variant summary

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

The NM_002691.4(POLD1):c.665C>A(p.Pro222Gln) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P222L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48

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.665C>A	p.Pro222Gln	missense_variant	6/27	ENST00000440232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD1	ENST00000440232.7	c.665C>A	p.Pro222Gln	missense_variant	6/27	1	NM_002691.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	24
Dann	Benign	0.97
DEOGEN2	Benign	0.38	T;.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;.;.;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D;.;.;.
REVEL	Benign	0.16
Sift	Benign	0.23	T;.;.;.
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.18	B;.;.;B
Vest4		0.65
MutPred		0.34		Gain of MoRF binding (P = 0.0369);Gain of MoRF binding (P = 0.0369);Gain of MoRF binding (P = 0.0369);Gain of MoRF binding (P = 0.0369);
MVP		0.64
MPC		0.71
ClinPred		0.95	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.36
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr19-50905537;