2-167126466-G-T

Position:

• chr2-167126466-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.409-9443G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,012 control chromosomes in the GnomAD database, including 9,003 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 0.29 (9003 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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-AS1 (HGNC:40679): (XIRP2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP2	NM_152381.6	c.409-9443G>T		intron_variant		ENST00000409195.6
XIRP2-AS1	NR_046665.1	n.155-1941C>A		intron_variant, non_coding_transcript_variant
XIRP2	NM_001079810.4	c.409-9443G>T		intron_variant
XIRP2	NM_001199143.2	c.409-9443G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6	c.409-9443G>T		intron_variant		5	NM_152381.6
XIRP2-AS1	ENST00000525330.1	n.155-1941C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44383 AN: 151894 Hom.: 8962 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.293 AC: 44488 AN: 152012 Hom.: 9003 Cov.: 32 AF XY: 0.291 AC XY: 21616 AN XY: 74294

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.272

Alfa AF: 0.176 Hom.: 1609

Bravo AF: 0.307

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.060
DANN	Benign	0.33

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: rs6432974; hg19: chr2-167982976; COSMIC: COSV54736975;