chr2-167006910-T-C

Position:

• chr2-167006910-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.408+103020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,502 control chromosomes in the GnomAD database, including 3,709 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 0.19 (3709 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.408+103020T>C		intron_variant		ENST00000409195.6	NP_689594.4
XIRP2	NM_001079810.4	c.408+103020T>C		intron_variant			NP_001073278.1
XIRP2	NM_001199143.2	c.408+103020T>C		intron_variant			NP_001186072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.408+103020T>C		intron_variant		5	NM_152381.6	ENSP00000386840
XIRP2	ENST00000409043.5	c.408+103020T>C		intron_variant		1		ENSP00000386454
XIRP2	ENST00000409728.5	c.408+103020T>C		intron_variant		1		ENSP00000386619
XIRP2	ENST00000672716.1	c.432+103020T>C		intron_variant				ENSP00000500725

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29023 AN: 151384 Hom.: 3687 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.192 AC: 29113 AN: 151502 Hom.: 3709 Cov.: 32 AF XY: 0.198 AC XY: 14675 AN XY: 74004

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.188

Alfa AF: 0.136 Hom.: 3516

Bravo AF: 0.202

Asia WGS AF: 0.417 AC: 1444 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.74

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: rs1877192; hg19: chr2-167863420;