rs869000

chr2-167006464-T-Cchr2-167006464-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152381.6(XIRP2):c.408+102574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,724 control chromosomes in the GnomAD database, including 2,331 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 0.15 (2331 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP2	NM_152381.6	c.408+102574T>C		intron_variant		ENST00000409195.6
XIRP2	NM_001079810.4	c.408+102574T>C		intron_variant
XIRP2	NM_001199143.2	c.408+102574T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6	c.408+102574T>C		intron_variant		5	NM_152381.6
XIRP2	ENST00000409043.5	c.408+102574T>C		intron_variant		1
XIRP2	ENST00000409728.5	c.408+102574T>C		intron_variant		1
XIRP2	ENST00000672716.1	c.432+102574T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22603 AN: 151606 Hom.: 2316 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.150 AC: 22684 AN: 151724 Hom.: 2331 Cov.: 32 AF XY: 0.155 AC XY: 11503 AN XY: 74146

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0915 Hom.: 1120

Bravo AF: 0.159

Asia WGS AF: 0.319 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.38
Dann	Benign	0.25

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: rs869000; hg19: chr2-167862974;