rs17733015

Positions:

• chr2-24286501-T-C
• chr2-24286501-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006277.3(ITSN2):​c.1724-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 565,334 control chromosomes in the GnomAD database, including 14,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3265 hom., cov: 32)
  • Exomes 𝑓: 0.22 (11233 hom.)
• Consequence: ITSN2 NM_006277.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.831

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-24286501-T-C is Benign according to our data. Variant chr2-24286501-T-C is described in ClinVar as [Benign]. Clinvar id is 1271628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN2	NM_006277.3	c.1724-150A>G		intron_variant		ENST00000355123.9	NP_006268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN2	ENST00000355123.9	c.1724-150A>G		intron_variant		1	NM_006277.3	ENSP00000347244.4
ITSN2	ENST00000361999.7	c.1724-150A>G		intron_variant		1		ENSP00000354561.2
ITSN2	ENST00000406921.7	c.1724-150A>G		intron_variant		1		ENSP00000384499.3
ITSN2	ENST00000412011.5	c.1799-150A>G		intron_variant		1		ENSP00000391224.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29289 AN: 152032 Hom.: 3264 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.221 AC: 91404 AN: 413184 Hom.: 11233 AF XY: 0.220 AC XY: 48479 AN XY: 219946

Gnomad4 AFR exome AF: 0.0964

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.0977

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.192 AC: 29288 AN: 152150 Hom.: 3265 Cov.: 32 AF XY: 0.188 AC XY: 14020 AN XY: 74392

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.184

Alfa AF: 0.242 Hom.: 5854

Bravo AF: 0.187

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.42

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: rs17733015; hg19: chr2-24509370; COSMIC: COSV61952857;