Variant 2-24208258-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006277.3(ITSN2):c.4657A>C(p.Lys1553Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00186 in 1,611,670 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 14 hom. )

Consequence

ITSN2
NM_006277.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.70

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016577125).

BP6

Variant 2-24208258-T-G is Benign according to our data. Variant chr2-24208258-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3055534.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITSN2	NM_006277.3 linkuse as main transcript	c.4657A>C	p.Lys1553Gln	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.4657A>C	p.Lys1553Gln	missense_variant	37/40	1	NM_006277.3	P2	Q9NZM3-1

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00336

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00192

AC:

482

AN:

250650

Hom.:

AF XY:

0.00195

AC XY:

264

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00184

AC:

2684

AN:

1459702

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1362

AN XY:

726200

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.000836

Gnomad4 FIN exome

AF:

0.00303

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

151968

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000868

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00336

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00351

Hom.:

Bravo

AF:

0.00159

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00212

AC:

257

EpiCase

AF:

0.00349

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ITSN2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2020

This variant is classified as likely 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.90

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.085

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;N;.

REVEL

Benign

0.14

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.22

T;T;T

Polyphen

0.011

B;B;.

Vest4

0.52

MVP

0.75

MPC

0.16

ClinPred

0.017

GERP RS

4.8

Varity_R

0.17

gMVP

0.37

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