Variant chr11-70820660-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012309.5(SHANK2):c.1197G>A(p.Ala399Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 696,650 control chromosomes in the GnomAD database, including 12,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2328 hom., cov: 33)

Exomes 𝑓: 0.18 ( 9942 hom. )

Consequence

SHANK2
NM_012309.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: -0.373

Variant links:

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]

SHANK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 11-70820660-C-T is Benign according to our data. Variant chr11-70820660-C-T is described in ClinVar as [Benign]. Clinvar id is 437876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.373 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHANK2	NM_012309.5 link	c.1197G>A	p.Ala399Ala	synonymous_variant	12/26	ENST00000601538.6	NP_036441.2	Q9UPX8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHANK2	ENST00000601538.6 link	c.1197G>A	p.Ala399Ala	synonymous_variant	12/26	5	NM_012309.5	ENSP00000469689.2		Q9UPX8-3

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23143

AN:

152058

Hom.:

2327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0776

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.170

AC:

22433

AN:

131582

Hom.:

2273

AF XY:

0.163

AC XY:

11505

AN XY:

70414

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0781

Gnomad SAS exome

AF:

0.0486

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.178

AC:

96698

AN:

544474

Hom.:

9942

Cov.:

AF XY:

0.171

AC XY:

49866

AN XY:

292360

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.0634

Gnomad4 SAS exome

AF:

0.0495

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.152

AC:

23142

AN:

152176

Hom.:

2328

Cov.:

AF XY:

0.150

AC XY:

11162

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0405

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.0778

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.192

Hom.:

3376

Bravo

AF:

0.149

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

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	Athena Diagnostics	Feb 27, 2018	- -

Autism

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Genetics Laboratory, Facudade de Medicina de Sao Jose do Rio Preto

Jan 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

6.4

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over