2-167181055-G-A

Variant names:

• chr2-167181055-G-A
• rs1429931
• NM_152381.6:c.563-29680G>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.563-29680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,134 control chromosomes in the GnomAD database, including 794 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 0.099 (794 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152381.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	NM_152381.6	MANE Select	c.563-29680G>A		intron	N/A	NP_689594.4
	XIRP2	NM_001199143.2		c.563-3487G>A		intron	N/A	NP_001186072.1
	XIRP2	NM_001079810.4		c.563-29680G>A		intron	N/A	NP_001073278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.563-29680G>A		intron	N/A	ENSP00000386840.2
	XIRP2	ENST00000409728.5	TSL:1	c.563-3487G>A		intron	N/A	ENSP00000386619.1
	XIRP2	ENST00000409043.5	TSL:1	c.563-29680G>A		intron	N/A	ENSP00000386454.1

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14970 AN: 152016 Hom.: 785 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0770

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0986 AC: 15001 AN: 152134 Hom.: 794 Cov.: 32 AF XY: 0.0966 AC XY: 7186 AN XY: 74394

African (AFR) AF: 0.133 AC: 5500 AN: 41474

American (AMR) AF: 0.0787 AC: 1203 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.0764 AC: 396 AN: 5180

South Asian (SAS) AF: 0.155 AC: 747 AN: 4820

European-Finnish (FIN) AF: 0.0391 AC: 414 AN: 10588

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0864 AC: 5877 AN: 67998

Other (OTH) AF: 0.106 AC: 223 AN: 2106

Alfa AF: 0.0960 Hom.: 83

Bravo AF: 0.102

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.33
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: rs1429931; hg19: chr2-168037565;