rs13132552

Variant names:

• chr4-185823620-T-C
• rs13132552
• ENST00000284776.11:c.-337-48254A>G

Variant summary

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

The ENST00000284776.11(SORBS2):​c.-337-48254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,332 control chromosomes in the GnomAD database, including 32,994 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 0.66 (32994 hom., cov: 31)
• Consequence: SORBS2 ENST00000284776.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 1 publications found

Genes affected

SORBS2 (HGNC:24098): (sorbin and SH3 domain containing 2) Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. They interact with the Arg/Abl binding proteins via the SH3 domains present in the carboxy end of the latter group of proteins. This gene encodes the sorbin and SH3 domain containing 2 protein. It has three C-terminal SH3 domains and an N-terminal sorbin homology (SoHo) domain that interacts with lipid raft proteins. The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that it functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SORBS2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000284776.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	NM_001394248.1		c.-172-48254A>G		intron	N/A	NP_001381177.1
	SORBS2	NM_001270771.3		c.-180-48254A>G		intron	N/A	NP_001257700.1
	SORBS2	NM_001394255.1		c.-168-48254A>G		intron	N/A	NP_001381184.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	ENST00000284776.11	TSL:1	c.-337-48254A>G		intron	N/A	ENSP00000284776.7
	SORBS2	ENST00000469627.1	TSL:1	n.154-48254A>G		intron	N/A
	SORBS2	ENST00000421420.6	TSL:4	c.-176-48254A>G		intron	N/A	ENSP00000393258.2

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99196 AN: 151214 Hom.: 32975 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.656 AC: 99266 AN: 151332 Hom.: 32994 Cov.: 31 AF XY: 0.651 AC XY: 48145 AN XY: 73944

African (AFR) AF: 0.673 AC: 27744 AN: 41198

American (AMR) AF: 0.677 AC: 10224 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1597 AN: 5104

South Asian (SAS) AF: 0.504 AC: 2415 AN: 4792

European-Finnish (FIN) AF: 0.683 AC: 7195 AN: 10538

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46163 AN: 67836

Other (OTH) AF: 0.664 AC: 1395 AN: 2100

Alfa AF: 0.667 Hom.: 56776

Bravo AF: 0.657

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13132552; hg19: chr4-186744774;