Variant 11-70471335-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_012309.5(SHANK2):c.*1533_*1534insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 398,676 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 1 hom. )

Consequence

SHANK2
NM_012309.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.143

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 -9 ACMG points.

BP6

Variant 11-70471335-C-CA is Benign according to our data. Variant chr11-70471335-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 305892.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00195 (296/151950) while in subpopulation AMR AF= 0.00386 (59/15270). AF 95% confidence interval is 0.00308. There are 4 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 296 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK2	NM_012309.5 linkuse as main transcript	c.1533_1534insT		3_prime_UTR_variant	26/26	ENST00000601538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHANK2	ENST00000601538.6 linkuse as main transcript	c.1533_1534insT		3_prime_UTR_variant	26/26	5	NM_012309.5	P1	Q9UPX8-3

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

294

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.00240

GnomAD4 exome

AF:

0.00229

AC:

566

AN:

246726

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

282

AN XY:

125050

show subpopulations

Gnomad4 AFR exome

AF:

0.000696

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00264

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.00273

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00195

AC:

296

AN:

151950

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

144

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00312

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autism spectrum disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SHANK2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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