rs2543662

chr2-24220402-C-A

Variant summary

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

The ENST00000406921.7(ITSN2):c.*492G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 983,806 control chromosomes in the GnomAD database, including 256,942 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 0.77 (45851 hom., cov: 33)
  • Exomes 𝑓: 0.71 (211091 hom.)
• Consequence: ITSN2 ENST00000406921.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

ITSN2 (HGNC:6184): (intersectin 2) This gene encodes a cytoplasmic protein which contains SH3 domains. This protein is a member of a family of proteins involved in clathrin-mediated endocytosis. Intersectin 2 is thought to regulate the formation of clathrin-coated vesicles and also may function in the induction of T cell antigen receptor (TCR) endocytosis. [provided by RefSeq, Jan 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITSN2	NM_006277.3	c.3699+543G>T		intron_variant		ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9	c.3699+543G>T		intron_variant		1	NM_006277.3	P2
	ENST00000662667.1	n.3777-918C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117715 AN: 152092 Hom.: 45814 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.712 AC: 591849 AN: 831596 Hom.: 211091 Cov.: 21 AF XY: 0.711 AC XY: 273056 AN XY: 384130

Gnomad4 AFR exome AF: 0.832

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.728

GnomAD4 genome AF: 0.774 AC: 117806 AN: 152210 Hom.: 45851 Cov.: 33 AF XY: 0.778 AC XY: 57922 AN XY: 74428

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.783

Alfa AF: 0.737 Hom.: 70925

Bravo AF: 0.778

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	5.1
Dann	Benign	0.79

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: rs2543662; hg19: chr2-24443271;