Variant chr2-24205292-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006277.3(ITSN2):c.4684T>A(p.Ser1562Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

ITSN2
NM_006277.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

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:

ITSN2 (HGNC:):

ITSN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3274667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITSN2	NM_006277.3 linkuse as main transcript	c.4684T>A	p.Ser1562Thr	missense_variant	38/40	ENST00000355123.9	NP_006268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITSN2	ENST00000355123.9 linkuse as main transcript	c.4684T>A	p.Ser1562Thr	missense_variant	38/40	1	NM_006277.3	ENSP00000347244.4		Q9NZM3-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.4684T>A (p.S1562T) alteration is located in exon 38 (coding exon 37) of the ITSN2 gene. This alteration results from a T to A substitution at nucleotide position 4684, causing the serine (S) at amino acid position 1562 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.064

.;T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

0.022

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.27

T;T;.

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.59

MutPred

0.22

.;Loss of phosphorylation at S1562 (P = 0.0578);.;

MVP

0.76

MPC

0.14

ClinPred

0.69

GERP RS

3.3

Varity_R

0.066

gMVP

0.35

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