2-24203682-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006277.3(ITSN2):c.5038G>A(p.Gly1680Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
ITSN2
NM_006277.3 missense
NM_006277.3 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 7.55
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITSN2 | NM_006277.3 | c.5038G>A | p.Gly1680Arg | missense_variant | 40/40 | ENST00000355123.9 | NP_006268.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251390Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727240
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74478
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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 | Jul 25, 2024 | The c.5038G>A (p.G1680R) alteration is located in exon 40 (coding exon 39) of the ITSN2 gene. This alteration results from a G to A substitution at nucleotide position 5038, causing the glycine (G) at amino acid position 1680 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
0.71
.;Gain of phosphorylation at T1679 (P = 0.1335);.;
MVP
MPC
0.18
ClinPred
D
GERP RS
Varity_R
gMVP
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