2-167184396-G-T

Variant names:

• chr2-167184396-G-T
• rs10497320
• NM_152381.6:c.563-26339G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000409195.6(XIRP2):​c.563-26339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000901 in 443,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: XIRP2 ENST00000409195.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409195.6. 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.563-26339G>T		intron	N/A	NP_689594.4
	XIRP2	NM_001199143.2		c.563-146G>T		intron	N/A	NP_001186072.1
	XIRP2	NM_001079810.4		c.563-26339G>T		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.563-26339G>T		intron	N/A	ENSP00000386840.2
	XIRP2	ENST00000409728.5	TSL:1	c.563-146G>T		intron	N/A	ENSP00000386619.1
	XIRP2	ENST00000409043.5	TSL:1	c.563-26339G>T		intron	N/A	ENSP00000386454.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000901 AC: 4 AN: 443906 Hom.: 0 AF XY: 0.00000853 AC XY: 2 AN XY: 234370

African (AFR) AF: 0.00 AC: 0 AN: 12006

American (AMR) AF: 0.00 AC: 0 AN: 16934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13274

East Asian (EAS) AF: 0.00 AC: 0 AN: 30408

South Asian (SAS) AF: 0.00 AC: 0 AN: 41528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3524

European-Non Finnish (NFE) AF: 0.0000152 AC: 4 AN: 262688

Other (OTH) AF: 0.00 AC: 0 AN: 25462

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.67
PhyloP100		-1.5

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: rs10497320; hg19: chr2-168040906;