Variant rs487989 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002689.4(POLA2):c.1747G>A(p.Gly583Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,582 control chromosomes in the GnomAD database, including 18,076 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1689 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16387 hom. )

Consequence

POLA2
NM_002689.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.239

Variant links:

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]

POLA2 links:

LOC105369344 (HGNC:):

LOC105369344 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.2425604E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLA2	NM_002689.4 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	18/18	ENST00000265465.8
LOC105369344	XR_007062727.1 linkuse as main transcript	n.1115-1595C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLA2	ENST00000265465.8 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	18/18	1	NM_002689.4	P1	Q14181-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21916

AN:

152082

Hom.:

1689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.0755

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.143

AC:

35797

AN:

250644

Hom.:

2754

AF XY:

0.145

AC XY:

19631

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.0854

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.0824

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.147

AC:

214672

AN:

1461382

Hom.:

16387

Cov.:

AF XY:

0.148

AC XY:

107925

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.0735

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.0851

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.144

AC:

21922

AN:

152200

Hom.:

1689

Cov.:

AF XY:

0.143

AC XY:

10634

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.0847

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.0755

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.137

Hom.:

3643

Bravo

AF:

0.150

TwinsUK

AF:

0.149

AC:

552

ALSPAC

AF:

0.147

AC:

567

ESP6500AA

AF:

0.175

AC:

769

ESP6500EA

AF:

0.142

AC:

1218

ExAC

AF:

0.143

AC:

17328

Asia WGS

AF:

0.130

AC:

452

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.2

DANN

Benign

0.88

DEOGEN2

Benign

0.18

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.42

MetaRNN

Benign

0.00072

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

REVEL

Benign

0.089

Sift

Benign

0.33

Sift4G

Benign

0.096

Polyphen

0.47

Vest4

0.013

MutPred

0.15

Gain of MoRF binding (P = 0.0328);

MPC

0.21

ClinPred

0.0053

GERP RS

-0.78

Varity_R

0.053

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over