rs10497321

Variant names:

• chr2-167217870-G-A
• rs10497321
• NM_152381.6:c.724-296G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152381.6(XIRP2):​c.724-296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,940 control chromosomes in the GnomAD database, including 2,144 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 0.15 (2144 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.724-296G>A		intron_variant	Intron 4 of 10	ENST00000409195.6	NP_689594.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.724-296G>A		intron_variant	Intron 4 of 10	5	NM_152381.6	ENSP00000386840.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22916 AN: 151824 Hom.: 2139 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.151 AC: 22952 AN: 151940 Hom.: 2144 Cov.: 32 AF XY: 0.151 AC XY: 11178 AN XY: 74262

African (AFR) AF: 0.267 AC: 11049 AN: 41386

American (AMR) AF: 0.126 AC: 1921 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3472

East Asian (EAS) AF: 0.112 AC: 578 AN: 5168

South Asian (SAS) AF: 0.147 AC: 707 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1410 AN: 10554

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0955 AC: 6490 AN: 67964

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.132 Hom.: 222

Bravo AF: 0.154

Asia WGS AF: 0.144 AC: 503 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.38
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10497321; hg19: chr2-168074380;