Variant 2-167184577-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000409728.5(XIRP2):c.598C>T(p.Leu200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 717,470 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 80 hom. )

Consequence

XIRP2
ENST00000409728.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.203

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029791594).

BP6

Variant 2-167184577-C-T is Benign according to our data. Variant chr2-167184577-C-T is described in ClinVar as [Benign]. Clinvar id is 789967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0109 (1654/152266) while in subpopulation EAS AF= 0.0522 (270/5174). AF 95% confidence interval is 0.0471. There are 20 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
XIRP2	NM_152381.6 linkuse as main transcript	c.563-26158C>T		intron_variant		ENST00000409195.6
XIRP2	NM_001199143.2 linkuse as main transcript	c.598C>T	p.Leu200Phe	missense_variant	4/11
XIRP2	NM_001079810.4 linkuse as main transcript	c.563-26158C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6 linkuse as main transcript	c.563-26158C>T		intron_variant		5	NM_152381.6		A4UGR9-8

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1658

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0523

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00984

AC:

1484

AN:

150854

Hom.:

AF XY:

0.00951

AC XY:

768

AN XY:

80756

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.00812

Gnomad ASJ exome

AF:

0.00333

Gnomad EAS exome

AF:

0.0560

Gnomad SAS exome

AF:

0.00439

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.00775

AC:

4381

AN:

565204

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

2199

AN XY:

304966

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.00853

Gnomad4 ASJ exome

AF:

0.00315

Gnomad4 EAS exome

AF:

0.0519

Gnomad4 SAS exome

AF:

0.00422

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0109

AC:

1654

AN:

152266

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

865

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0522

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.00201

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00714

AC:

153

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

XIRP2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.6

DANN

Benign

0.53

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-0.23

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

0.0040

Vest4

0.045

MVP

0.014

ClinPred

0.0016

GERP RS

-4.6

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