Variant 2-167184642-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBA1

The ENST00000409728.5(XIRP2):c.661+2T>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 716,532 control chromosomes in the GnomAD database, including 3,835 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 797 hom., cov: 32)

Exomes 𝑓: 0.095 ( 3038 hom. )

Consequence

XIRP2
ENST00000409728.5 splice_donor

Scores

Splicing: ADA: 0.00004544

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.555

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.03360768 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 2-167184642-T-C is Benign according to our data. Variant chr2-167184642-T-C is described in ClinVar as [Benign]. Clinvar id is 3056174.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
XIRP2	NM_152381.6 linkuse as main transcript	c.563-26093T>C	intron_variant	ENST00000409195.6
XIRP2	NM_001199143.2 linkuse as main transcript	c.661+2T>C	splice_donor_variant
XIRP2	NM_001079810.4 linkuse as main transcript	c.563-26093T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6 linkuse as main transcript	c.563-26093T>C		intron_variant		5	NM_152381.6		A4UGR9-8

Frequencies

GnomAD3 genomes

AF:

0.0984

AC:

14958

AN:

152054

Hom.:

788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.0786

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.0389

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0865

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0938

AC:

14066

AN:

149940

Hom.:

794

AF XY:

0.101

AC XY:

8141

AN XY:

80378

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0530

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.0822

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.0426

Gnomad NFE exome

AF:

0.0891

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0945

AC:

53339

AN:

564360

Hom.:

3038

Cov.:

AF XY:

0.100

AC XY:

30472

AN XY:

304570

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0552

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0573

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.0900

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0985

AC:

14989

AN:

152172

Hom.:

797

Cov.:

AF XY:

0.0965

AC XY:

7181

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.0786

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0771

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0389

Gnomad4 NFE

AF:

0.0865

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0941

Hom.:

958

Bravo

AF:

0.102

TwinsUK

AF:

0.0844

AC:

313

ALSPAC

AF:

0.0784

AC:

302

ExAC

AF:

0.115

AC:

2377

Asia WGS

AF:

0.107

AC:

373

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

XIRP2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

Cadd

Benign

6.4

Dann

Benign

0.27

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.011

MutationTaster

Benign

1.0

P;P;P;P;P;P

GERP RS

-1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000045

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.060

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