rs948195

Positions:

• chr11-70578201-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012309.5(SHANK2):​c.2062-75270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,128 control chromosomes in the GnomAD database, including 48,287 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 0.79 (48287 hom., cov: 32)
• Consequence: SHANK2 NM_012309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK2	NM_012309.5	c.2062-75270G>A		intron_variant		ENST00000601538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHANK2	ENST00000601538.6	c.2062-75270G>A		intron_variant		5	NM_012309.5	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120815 AN: 152010 Hom.: 48243 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.795 AC: 120915 AN: 152128 Hom.: 48287 Cov.: 32 AF XY: 0.801 AC XY: 59539 AN XY: 74356

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.798

Alfa AF: 0.799 Hom.: 22957

Bravo AF: 0.788

Asia WGS AF: 0.806 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.060
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs948195; hg19: chr11-70424306;