rs10497320

Positions:

• chr2-167184396-G-A
• chr2-167184396-G-T

Variant summary

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

The NM_152381.6(XIRP2):​c.563-26339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 595,792 control chromosomes in the GnomAD database, including 2,797 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 0.080 (533 hom., cov: 32)
  • Exomes 𝑓: 0.092 (2264 hom.)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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.563-26339G>A		intron_variant		ENST00000409195.6	NP_689594.4
XIRP2	NM_001079810.4	c.563-26339G>A		intron_variant			NP_001073278.1
XIRP2	NM_001199143.2	c.563-146G>A		intron_variant			NP_001186072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.563-26339G>A		intron_variant		5	NM_152381.6	ENSP00000386840

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12106 AN: 152030 Hom.: 530 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.0982

GnomAD4 exome AF: 0.0915 AC: 40611 AN: 443644 Hom.: 2264 AF XY: 0.0969 AC XY: 22706 AN XY: 234214

Gnomad4 AFR exome AF: 0.0741

Gnomad4 AMR exome AF: 0.0602

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0565

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.0991

GnomAD4 genome AF: 0.0796 AC: 12116 AN: 152148 Hom.: 533 Cov.: 32 AF XY: 0.0793 AC XY: 5897 AN XY: 74380

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0832 Hom.: 159

Bravo AF: 0.0802

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.67

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: rs10497320; hg19: chr2-168040906;