NM_002689.4:c.1150G>T

Variant names:

• chr11-65289068-G-T
• rs760274602
• NM_002689.4:c.1150G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002689.4(POLA2):​c.1150G>T​(p.Ala384Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: POLA2 NM_002689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

Genes affected

POLA2 (HGNC:30073): (DNA polymerase alpha 2, accessory subunit) Predicted to enable DNA binding activity. Involved in DNA replication, synthesis of RNA primer. Located in cytosol and nucleoplasm. Part of alpha DNA polymerase:primase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285816 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20203304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLA2	NM_002689.4	c.1150G>T	p.Ala384Ser	missense_variant	Exon 12 of 18	ENST00000265465.8	NP_002680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLA2	ENST00000265465.8	c.1150G>T	p.Ala384Ser	missense_variant	Exon 12 of 18	1	NM_002689.4	ENSP00000265465.3
ENSG00000285816	ENST00000649896.1	n.1150G>T		non_coding_transcript_exon_variant	Exon 12 of 20			ENSP00000498025.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.020	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.10
Sift	Benign	0.51	T
Sift4G	Benign	0.73	T
Polyphen		0.53	P
Vest4		0.10
MutPred		0.49		Loss of catalytic residue at A384 (P = 0.0429);
MVP		0.40
MPC		0.18
ClinPred		0.64	D
GERP RS		5.4
Varity_R		0.39
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs760274602; hg19: chr11-65056539;