Variant chr2-167250981-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_152381.6(XIRP2):c.9589A>G(p.Ile3197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,492 control chromosomes in the GnomAD database, including 15,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2754 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12637 hom. )

Consequence

XIRP2
NM_152381.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.272

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 (HGNC:):

XIRP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042324364).

BP6

Variant 2-167250981-A-G is Benign according to our data. Variant chr2-167250981-A-G is described in ClinVar as [Benign]. Clinvar id is 3055980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-167250981-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP2	NM_152381.6 linkuse as main transcript	c.9589A>G	p.Ile3197Val	missense_variant	9/11	ENST00000409195.6	NP_689594.4	A4UGR9-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6 linkuse as main transcript	c.9589A>G	p.Ile3197Val	missense_variant	9/11	5	NM_152381.6	ENSP00000386840.2		A4UGR9-8

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26182

AN:

151812

Hom.:

2743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.170

GnomAD3 exomes

AF:

0.144

AC:

35799

AN:

248954

Hom.:

2965

AF XY:

0.145

AC XY:

19548

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.124

AC:

181244

AN:

1461562

Hom.:

12637

Cov.:

AF XY:

0.126

AC XY:

91258

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.173

AC:

26231

AN:

151930

Hom.:

2754

Cov.:

AF XY:

0.173

AC XY:

12815

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.125

Hom.:

3227

Bravo

AF:

0.176

TwinsUK

AF:

0.105

AC:

391

ALSPAC

AF:

0.118

AC:

454

ESP6500AA

AF:

0.278

AC:

1086

ESP6500EA

AF:

0.111

AC:

924

ExAC

AF:

0.148

AC:

17889

Asia WGS

AF:

0.173

AC:

603

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIRP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 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

0.076

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.16

DANN

Benign

0.23

DEOGEN2

Benign

0.012

.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.97

.;L;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.040

N;.;N;.

REVEL

Benign

0.011

Sift

Benign

0.26

T;.;T;.

Sift4G

Benign

0.89

.;.;.;T

Polyphen

0.0010

.;B;B;.

Vest4

0.048

MPC

0.019

ClinPred

0.0075

GERP RS

-4.1

Varity_R

0.018

gMVP

0.15

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