Variant rs532411 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_199420.4(POLQ):c.6911C>T(p.Ala2304Val) variant causes a missense change. The variant allele was found at a frequency of 0.067 in 1,613,214 control chromosomes in the GnomAD database, including 4,717 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2304S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.098 ( 1064 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3653 hom. )

Consequence

POLQ
NM_199420.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.47

Variant links:

Genes affected

POLQ (HGNC:9186): (DNA polymerase theta) Enables catalytic activity, acting on DNA; chromatin binding activity; and identical protein binding activity. Involved in DNA repair; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POLQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010478795).

BP6

Variant 3-121467575-G-A is Benign according to our data. Variant chr3-121467575-G-A is described in ClinVar as [Benign]. Clinvar id is 3055919.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLQ	NM_199420.4 linkuse as main transcript	c.6911C>T	p.Ala2304Val	missense_variant	24/30	ENST00000264233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLQ	ENST00000264233.6 linkuse as main transcript	c.6911C>T	p.Ala2304Val	missense_variant	24/30	1	NM_199420.4	P1	O75417-1
POLQ	ENST00000474243.1 linkuse as main transcript	n.412C>T		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14910

AN:

152134

Hom.:

1059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0593

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0688

Gnomad OTH

AF:

0.0955

GnomAD3 exomes

AF:

0.0613

AC:

15382

AN:

250860

Hom.:

727

AF XY:

0.0569

AC XY:

7715

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0406

Gnomad ASJ exome

AF:

0.0776

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0129

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.0702

Gnomad OTH exome

AF:

0.0615

GnomAD4 exome

AF:

0.0638

AC:

93152

AN:

1460962

Hom.:

3653

Cov.:

AF XY:

0.0619

AC XY:

44985

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.0435

Gnomad4 ASJ exome

AF:

0.0784

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0663

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.0981

AC:

14934

AN:

152252

Hom.:

1064

Cov.:

AF XY:

0.0952

AC XY:

7085

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.0786

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0593

Gnomad4 NFE

AF:

0.0687

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.0719

Hom.:

1148

Bravo

AF:

0.103

TwinsUK

AF:

0.0685

AC:

254

ALSPAC

AF:

0.0646

AC:

249

ESP6500AA

AF:

0.201

AC:

887

ESP6500EA

AF:

0.0638

AC:

549

ExAC

AF:

0.0653

AC:

7927

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0688

EpiControl

AF:

0.0658

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

POLQ-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.12

Sift

Benign

0.037

.;D

Sift4G

Benign

0.10

T;T

Polyphen

0.49

.;P

Vest4

0.022

MPC

0.13

ClinPred

0.016

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over