rs1783606

Variant names:

• chr11-70730546-C-T
• rs1783606
• NM_012309.5:c.1778-31783G>A

Variant summary

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

The NM_012309.5(SHANK2):​c.1778-31783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,212 control chromosomes in the GnomAD database, including 2,149 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 0.16 (2149 hom., cov: 32)
• Consequence: SHANK2 NM_012309.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autism, susceptibility to, 17

  Inheritance: AD Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012309.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHANK2	NM_012309.5	MANE Select	c.1778-31783G>A		intron	N/A	NP_036441.2	Q9UPX8-3
	SHANK2	NM_001441024.1		c.1949-31783G>A		intron	N/A	NP_001427953.1
	SHANK2	NM_001441025.1		c.1778-31783G>A		intron	N/A	NP_001427954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHANK2	ENST00000601538.6	TSL:5 MANE Select	c.1778-31783G>A		intron	N/A	ENSP00000469689.2	Q9UPX8-3
	SHANK2	ENST00000916035.1		c.1778-31783G>A		intron	N/A	ENSP00000586094.1
	SHANK2	ENST00000916037.1		c.1778-31783G>A		intron	N/A	ENSP00000586096.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23715 AN: 152094 Hom.: 2143 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.156 AC: 23750 AN: 152212 Hom.: 2149 Cov.: 32 AF XY: 0.157 AC XY: 11692 AN XY: 74426

African (AFR) AF: 0.215 AC: 8927 AN: 41508

American (AMR) AF: 0.111 AC: 1696 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3470

East Asian (EAS) AF: 0.0477 AC: 246 AN: 5160

South Asian (SAS) AF: 0.293 AC: 1417 AN: 4834

European-Finnish (FIN) AF: 0.0958 AC: 1017 AN: 10614

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9090 AN: 68002

Other (OTH) AF: 0.164 AC: 348 AN: 2116

Alfa AF: 0.153 Hom.: 1241

Bravo AF: 0.155

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.55
PhyloP100		-0.26
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: rs1783606; hg19: chr11-70576651;