Variant 11-70470286-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012309.5(SHANK2):c.*2583T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,310 control chromosomes in the GnomAD database, including 6,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6308 hom., cov: 33)

Exomes 𝑓: 0.34 ( 4 hom. )

Consequence

SHANK2
NM_012309.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.266

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:

SHANK2 (HGNC:):

SHANK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-70470286-A-G is Benign according to our data. Variant chr11-70470286-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 305889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHANK2	NM_012309.5 linkuse as main transcript	c.*2583T>C		3_prime_UTR_variant	26/26	ENST00000601538.6	NP_036441.2	Q9UPX8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHANK2	ENST00000601538 linkuse as main transcript	c.*2583T>C		3_prime_UTR_variant	26/26	5	NM_012309.5	ENSP00000469689.2		Q9UPX8-3

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41491

AN:

152124

Hom.:

6302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.338

AC:

AN:

Hom.:

Cov.:

AF XY:

0.316

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.273

AC:

41494

AN:

152242

Hom.:

6308

Cov.:

AF XY:

0.272

AC XY:

20235

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.178

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.298

Hom.:

1617

Bravo

AF:

0.269

Asia WGS

AF:

0.182

AC:

637

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autism spectrum disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.32

DANN

Benign

0.47

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