Variant chr2-167243228-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_152381.6(XIRP2):c.1836T>C(p.Gly612Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,762 control chromosomes in the GnomAD database, including 36,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 7638 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29249 hom. )

Consequence

XIRP2
NM_152381.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.321

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-167243228-T-C is Benign according to our data. Variant chr2-167243228-T-C is described in ClinVar as [Benign]. Clinvar id is 3058991.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-167243228-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.321 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 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.1836T>C	p.Gly612Gly	synonymous_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.1836T>C	p.Gly612Gly	synonymous_variant	9/11	5	NM_152381.6	ENSP00000386840.2		A4UGR9-8

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42180

AN:

151860

Hom.:

7605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.225

AC:

56032

AN:

249314

Hom.:

7448

AF XY:

0.222

AC XY:

29981

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.303

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.185

AC:

271133

AN:

1461784

Hom.:

29249

Cov.:

AF XY:

0.187

AC XY:

135920

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.278

AC:

42273

AN:

151978

Hom.:

7638

Cov.:

AF XY:

0.279

AC XY:

20756

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.196

Hom.:

3957

Bravo

AF:

0.287

Asia WGS

AF:

0.339

AC:

1181

AN:

3478

EpiCase

AF:

0.158

EpiControl

AF:

0.148

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

Oct 21, 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

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.3

DANN

Benign

0.55

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