rs10497304

Variant names:

• chr2-166967665-A-T
• rs10497304
• NM_152381.6:c.408+63775A>T

Variant summary

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

The NM_152381.6(XIRP2):​c.408+63775A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,038 control chromosomes in the GnomAD database, including 116 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 0.037 (116 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.408+63775A>T		intron_variant	Intron 2 of 10	ENST00000409195.6	NP_689594.4
XIRP2	NM_001199143.2	c.408+63775A>T		intron_variant	Intron 2 of 10		NP_001186072.1
XIRP2	NM_001079810.4	c.408+63775A>T		intron_variant	Intron 2 of 9		NP_001073278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.408+63775A>T		intron_variant	Intron 2 of 10	5	NM_152381.6	ENSP00000386840.2
XIRP2	ENST00000409728.5	c.408+63775A>T		intron_variant	Intron 2 of 10	1		ENSP00000386619.1
XIRP2	ENST00000409043.5	c.408+63775A>T		intron_variant	Intron 2 of 9	1		ENSP00000386454.1
XIRP2	ENST00000672716.1	c.432+63775A>T		intron_variant	Intron 2 of 9			ENSP00000500725.1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5546 AN: 151922 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0365 AC: 5555 AN: 152038 Hom.: 116 Cov.: 32 AF XY: 0.0361 AC XY: 2684 AN XY: 74320

African (AFR) AF: 0.0166 AC: 687 AN: 41500

American (AMR) AF: 0.0476 AC: 726 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3466

East Asian (EAS) AF: 0.0607 AC: 312 AN: 5144

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4832

European-Finnish (FIN) AF: 0.0295 AC: 313 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3173 AN: 67920

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0425 Hom.: 19

Bravo AF: 0.0363

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

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: rs10497304; hg19: chr2-167824175;