2-167126466-G-T

Variant names:

• chr2-167126466-G-T
• rs6432974
• NM_152381.6:c.409-9443G>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.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
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	NM_152381.6	MANE Select	c.409-9443G>T		intron	N/A	NP_689594.4
	XIRP2	NM_001199143.2		c.409-9443G>T		intron	N/A	NP_001186072.1	A4UGR9-6
	XIRP2	NM_001079810.4		c.409-9443G>T		intron	N/A	NP_001073278.1	A4UGR9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.409-9443G>T		intron	N/A	ENSP00000386840.2	A4UGR9-8
	XIRP2	ENST00000409728.5	TSL:1	c.409-9443G>T		intron	N/A	ENSP00000386619.1	A4UGR9-6
	XIRP2	ENST00000409043.5	TSL:1	c.409-9443G>T		intron	N/A	ENSP00000386454.1	A4UGR9-4

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

African (AFR) AF: 0.574 AC: 23782 AN: 41412

American (AMR) AF: 0.210 AC: 3207 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1893 AN: 5152

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4814

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10600

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10772 AN: 67992

Other (OTH) AF: 0.272 AC: 572 AN: 2106

Alfa AF: 0.180 Hom.: 1856

Bravo AF: 0.307

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.060
DANN	Benign	0.33
PhyloP100		-2.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6432974;

hg19: chr2-167982976;

COSMIC: COSV54736975;