rs200213968
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2
The NM_012309.5(SHANK2):c.3299C>T(p.Pro1100Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,611,002 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 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SHANK2
NM_012309.5 missense
NM_012309.5 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 5.05
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26787516).
BP6
?
Variant 11-70486994-G-A is Benign according to our data. Variant chr11-70486994-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212161.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHANK2 | NM_012309.5 | c.3299C>T | p.Pro1100Leu | missense_variant | 25/26 | ENST00000601538.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHANK2 | ENST00000601538.6 | c.3299C>T | p.Pro1100Leu | missense_variant | 25/26 | 5 | NM_012309.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000864 AC: 21AN: 243104Hom.: 0 AF XY: 0.0000826 AC XY: 11AN XY: 133142
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GnomAD4 exome AF: 0.000112 AC: 164AN: 1458824Hom.: 0 Cov.: 34 AF XY: 0.000103 AC XY: 75AN XY: 725840
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74332
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 17, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Benign
T;T;T;T;T
Polyphen
1.0
.;.;.;.;D
Vest4
MVP
MPC
0.53
ClinPred
T
GERP RS
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