rs782245412
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_012309.5(SHANK2):c.3120C>T(p.Ser1040=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
SHANK2
NM_012309.5 synonymous
NM_012309.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.34
Genes affected
SHANK2 (HGNC:14295): (SH3 and multiple ankyrin repeat domains 2) This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density of excitatory synapses. Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, and an SH3 domain. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the postsynaptic densities of the adult and developing brain. Alterations in the encoded protein may be associated with susceptibility to autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 11-70487173-G-A is Benign according to our data. Variant chr11-70487173-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.34 with no splicing effect.
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHANK2 | NM_012309.5 | c.3120C>T | p.Ser1040= | synonymous_variant | 25/26 | ENST00000601538.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHANK2 | ENST00000601538.6 | c.3120C>T | p.Ser1040= | synonymous_variant | 25/26 | 5 | NM_012309.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000124 AC: 31AN: 250986Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135776
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GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461150Hom.: 0 Cov.: 34 AF XY: 0.0000550 AC XY: 40AN XY: 726910
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 15, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | SHANK2: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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