rs2303296

Variant summary

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

The NM_006277.3(ITSN2):ā€‹c.4321T>Cā€‹(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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.18 ( 3122 hom., cov: 31)
Exomes š‘“: 0.25 ( 46965 hom. )

Consequence

ITSN2
NM_006277.3 synonymous

Scores

2

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]

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
ITSN2NM_006277.3 linkuse as main transcriptc.4321T>C p.Leu1441= synonymous_variant 35/40 ENST00000355123.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITSN2ENST00000355123.9 linkuse as main transcriptc.4321T>C p.Leu1441= synonymous_variant 35/401 NM_006277.3 P2Q9NZM3-1
ITSN2ENST00000361999.7 linkuse as main transcriptc.4240T>C p.Leu1414= synonymous_variant 34/391 A2Q9NZM3-2
ITSN2ENST00000479575.1 linkuse as main transcriptn.360T>C non_coding_transcript_exon_variant 1/45
ITSN2ENST00000427234.5 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.180
AC:
27360
AN:
152044
Hom.:
3121
Cov.:
31
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.:
34
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.:
31
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 17, 2021- -
ITSN2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 31, 2020This 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.

Other links and lift over

dbSNP: rs2303296; hg19: chr2-24432839; API