12-26210970-A-G

Variant names:

• chr12-26210970-A-G
• rs2291138
• NM_005086.5:c.280-13323A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005086.5(SSPN):​c.280-13323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SSPN NM_005086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 3 publications found

Genes affected

SSPN (HGNC:11322): (sarcospan) This gene encodes a member of the dystrophin-glycoprotein complex (DGC). The DGC spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Two alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ITPR2-AS1 (HGNC:56072): (ITPR2 and SSPN antisense RNA 1)

ENSG00000255750 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSPN	NM_005086.5	c.280-13323A>G		intron_variant	Intron 1 of 2	ENST00000242729.7	NP_005077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSPN	ENST00000242729.7	c.280-13323A>G		intron_variant	Intron 1 of 2	1	NM_005086.5	ENSP00000242729.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.69
PhyloP100		-0.39

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: rs2291138; hg19: chr12-26363903;