Variant chr2-24208315-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006277.3(ITSN2):c.4600G>A(p.Ala1534Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,610,200 control chromosomes in the GnomAD database, including 48,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 3036 hom., cov: 31)

Exomes 𝑓: 0.24 ( 45220 hom. )

Consequence

ITSN2
NM_006277.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.39

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022797585).

BP6

Variant 2-24208315-C-T is Benign according to our data. Variant chr2-24208315-C-T is described in ClinVar as [Benign]. Clinvar id is 1240643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 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.4600G>A	p.Ala1534Thr	missense_variant	37/40	ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9 linkuse as main transcript	c.4600G>A	p.Ala1534Thr	missense_variant	37/40	1	NM_006277.3	P2	Q9NZM3-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

26950

AN:

151830

Hom.:

3035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.197

AC:

49356

AN:

250018

Hom.:

5485

AF XY:

0.204

AC XY:

27532

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.242

AC:

352831

AN:

1458250

Hom.:

45220

Cov.:

AF XY:

0.241

AC XY:

174973

AN XY:

725616

show subpopulations

Gnomad4 AFR exome

AF:

0.0500

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.177

AC:

26949

AN:

151950

Hom.:

3036

Cov.:

AF XY:

0.174

AC XY:

12945

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.229

Hom.:

6761

Bravo

AF:

0.170

TwinsUK

AF:

0.268

AC:

993

ALSPAC

AF:

0.269

AC:

1037

ESP6500AA

AF:

0.0592

AC:

261

ESP6500EA

AF:

0.242

AC:

2084

ExAC

AF:

0.196

AC:

23826

Asia WGS

AF:

0.139

AC:

487

AN:

3478

EpiCase

AF:

0.252

EpiControl

AF:

0.251

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	May 12, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

.;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

.;L;.

MutationTaster

Benign

1.5e-7

P;P;P

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.16

T;T;.

Sift4G

Benign

0.22

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.35

MPC

0.14

ClinPred

0.020

GERP RS

4.9

Varity_R

0.10

gMVP

0.49

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

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