Variant 2-24209970-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006277.3(ITSN2):c.4321T>C(p.Leu1441=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,613,620 control chromosomes in the GnomAD database, including 50,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3122 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46965 hom. )

Consequence

ITSN2
NM_006277.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0520

Variant links:

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]

ITSN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-24209970-A-G is Benign according to our data. Variant chr2-24209970-A-G is described in ClinVar as [Benign]. Clinvar id is 1251753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

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	UniProt
ITSN2	NM_006277.3 linkuse as main transcript	c.4321T>C	p.Leu1441=	synonymous_variant	35/40	ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9 linkuse as main transcript	c.4321T>C	p.Leu1441=	synonymous_variant	35/40	1	NM_006277.3	P2	Q9NZM3-1
ITSN2	ENST00000361999.7 linkuse as main transcript	c.4240T>C	p.Leu1414=	synonymous_variant	34/39	1		A2	Q9NZM3-2
ITSN2	ENST00000479575.1 linkuse as main transcript	n.360T>C		non_coding_transcript_exon_variant	1/4	5
ITSN2	ENST00000427234.5 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27360

AN:

152044

Hom.:

3121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.200

AC:

50268

AN:

251492

Hom.:

5675

AF XY:

0.206

AC XY:

28014

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.246

AC:

360241

AN:

1461456

Hom.:

46965

Cov.:

AF XY:

0.246

AC XY:

178544

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.180

AC:

27355

AN:

152164

Hom.:

3122

Cov.:

AF XY:

0.177

AC XY:

13137

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.239

Hom.:

6774

Bravo

AF:

0.172

Asia WGS

AF:

0.141

AC:

492

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.255

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Mar 17, 2021	- -

ITSN2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.8

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over