Variant chr2-167135961-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_152381.6(XIRP2):c.461G>A(p.Gly154Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,610,900 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 8 hom. )

Consequence

XIRP2
NM_152381.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

XIRP2 (HGNC:14303): (xin actin binding repeat containing 2) Enables actin filament binding activity. Predicted to be involved in actin cytoskeleton organization and heart development. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Colocalizes with focal adhesion and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

XIRP2 links:

XIRP2-AS1 (HGNC:40679): (XIRP2 antisense RNA 1)

XIRP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040955544).

BP6

Variant 2-167135961-G-A is Benign according to our data. Variant chr2-167135961-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049522.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
XIRP2	NM_152381.6 linkuse as main transcript	c.461G>A	p.Gly154Glu	missense_variant	3/11	ENST00000409195.6
XIRP2-AS1	NR_046665.1 linkuse as main transcript	n.154+4841C>T		intron_variant, non_coding_transcript_variant
XIRP2	NM_001199143.2 linkuse as main transcript	c.461G>A	p.Gly154Glu	missense_variant	3/11
XIRP2	NM_001079810.4 linkuse as main transcript	c.461G>A	p.Gly154Glu	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6 linkuse as main transcript	c.461G>A	p.Gly154Glu	missense_variant	3/11	5	NM_152381.6		A4UGR9-8
XIRP2-AS1	ENST00000525330.1 linkuse as main transcript	n.154+4841C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000750

AC:

185

AN:

246538

Hom.:

AF XY:

0.00103

AC XY:

138

AN XY:

133894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00603

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000320

AC:

467

AN:

1458844

Hom.:

Cov.:

AF XY:

0.000482

AC XY:

350

AN XY:

725764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00520

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000171

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000416

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000894

AC:

108

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIRP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

This variant is classified as likely 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

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.0

DANN

Uncertain

0.99

Eigen

Benign

-0.040

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.99

N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.8

D;N;N

REVEL

Benign

0.095

Sift

Benign

0.061

T;T;T

Sift4G

Benign

0.13

T;T;.

Polyphen

0.62

P;P;.

Vest4

0.22

MutPred

0.14

Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);

MVP

0.46

MPC

0.021

ClinPred

0.095

GERP RS

4.6

gMVP

0.014

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