rs2303296
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006277.3(ITSN2):āc.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
NM_006277.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0520
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]
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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 | 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 | c.4321T>C | p.Leu1441= | synonymous_variant | 35/40 | 1 | NM_006277.3 | P2 | |
ITSN2 | ENST00000361999.7 | c.4240T>C | p.Leu1414= | synonymous_variant | 34/39 | 1 | A2 | ||
ITSN2 | ENST00000479575.1 | n.360T>C | non_coding_transcript_exon_variant | 1/4 | 5 | ||||
ITSN2 | ENST00000427234.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.180 AC: 27360AN: 152044Hom.: 3121 Cov.: 31
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GnomAD3 exomes AF: 0.200 AC: 50268AN: 251492Hom.: 5675 AF XY: 0.206 AC XY: 28014AN XY: 135920
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GnomAD4 exome AF: 0.246 AC: 360241AN: 1461456Hom.: 46965 Cov.: 34 AF XY: 0.246 AC XY: 178544AN XY: 727048
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GnomAD4 genome AF: 0.180 AC: 27355AN: 152164Hom.: 3122 Cov.: 31 AF XY: 0.177 AC XY: 13137AN XY: 74394
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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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at