rs6706115

Positions:

• chr2-167181483-T-A
• chr2-167181483-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152381.6(XIRP2):​c.563-29252T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,262 control chromosomes in the GnomAD database, including 795 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (795 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.563-29252T>A		intron_variant		ENST00000409195.6	NP_689594.4
XIRP2	NM_001199143.2	c.563-3059T>A		intron_variant			NP_001186072.1
XIRP2	NM_001079810.4	c.563-29252T>A		intron_variant			NP_001073278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.563-29252T>A		intron_variant		5	NM_152381.6	ENSP00000386840.2

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14979 AN: 152144 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0986 AC: 15010 AN: 152262 Hom.: 795 Cov.: 32 AF XY: 0.0966 AC XY: 7191 AN XY: 74460

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0437 Hom.: 29

Bravo AF: 0.102

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs6706115; hg19: chr2-168037993;