11-70468767-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012309.5(SHANK2):c.*4102C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 152,256 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (149 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHANK2 NM_012309.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.635

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-70468767-G-C is Benign according to our data. Variant chr11-70468767-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 305882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK2	NM_012309.5	c.*4102C>G		3_prime_UTR_variant	26/26	ENST00000601538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHANK2	ENST00000601538.6	c.*4102C>G		3_prime_UTR_variant	26/26	5	NM_012309.5	P1
SHANK2	ENST00000409161.5	c.*4102C>G		3_prime_UTR_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5432 AN: 152138 Hom.: 149 Cov.: 33

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0370

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0357 AC: 5434 AN: 152256 Hom.: 149 Cov.: 33 AF XY: 0.0333 AC XY: 2480 AN XY: 74436

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0168 Hom.: 6

Bravo AF: 0.0362

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.9
Dann	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61885874; hg19: chr11-70314872;