11-71221898-A-G

Position:

• chr11-71221898-A-G

Variant summary

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

The NM_012309.5(SHANK2):​c.-13+2799T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,922 control chromosomes in the GnomAD database, including 24,353 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 (24353 hom., cov: 31)
• Consequence: SHANK2 NM_012309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK2	NM_012309.5	c.-13+2799T>C		intron_variant		ENST00000601538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHANK2	ENST00000601538.6	c.-13+2799T>C		intron_variant		5	NM_012309.5	P1
SHANK2	ENST00000482659.2	n.229+2799T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80324 AN: 151804 Hom.: 24288 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.530 AC: 80456 AN: 151922 Hom.: 24353 Cov.: 31 AF XY: 0.532 AC XY: 39498 AN XY: 74220

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.488

Alfa AF: 0.400 Hom.: 22215

Bravo AF: 0.542

Asia WGS AF: 0.553 AC: 1922 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	0.59
DANN	Benign	0.15

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: rs2919732; hg19: chr11-70932944;