11-70632453-T-C

Variant names:

• chr11-70632453-T-C
• rs1207142
• NM_012309.5:c.2061+27375A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012309.5(SHANK2):​c.2061+27375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,984 control chromosomes in the GnomAD database, including 21,499 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21499 hom., cov: 32)
• Consequence: SHANK2 NM_012309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 2 publications found

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-AS1 (HGNC:40014): (SHANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHANK2	NM_012309.5	c.2061+27375A>G		intron_variant	Intron 17 of 25	ENST00000601538.6	NP_036441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHANK2	ENST00000601538.6	c.2061+27375A>G		intron_variant	Intron 17 of 25	5	NM_012309.5	ENSP00000469689.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80363 AN: 151866 Hom.: 21496 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.529 AC: 80400 AN: 151984 Hom.: 21499 Cov.: 32 AF XY: 0.524 AC XY: 38948 AN XY: 74300

African (AFR) AF: 0.494 AC: 20442 AN: 41412

American (AMR) AF: 0.492 AC: 7519 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1663 AN: 5176

South Asian (SAS) AF: 0.540 AC: 2600 AN: 4814

European-Finnish (FIN) AF: 0.474 AC: 5001 AN: 10556

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38898 AN: 67972

Other (OTH) AF: 0.562 AC: 1183 AN: 2106

Alfa AF: 0.569 Hom.: 14747

Bravo AF: 0.528

Asia WGS AF: 0.399 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1207142; hg19: chr11-70478558;