rs13132552

Positions:

• chr4-185823620-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS2	NM_001270771.3	c.-180-48254A>G		intron_variant			NP_001257700.1
SORBS2	NM_001394248.1	c.-172-48254A>G		intron_variant			NP_001381177.1
SORBS2	NM_001394255.1	c.-168-48254A>G		intron_variant			NP_001381184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000284776.11	c.-337-48254A>G		intron_variant		1		ENSP00000284776
SORBS2	ENST00000469627.1	n.154-48254A>G		intron_variant, non_coding_transcript_variant		1
SORBS2	ENST00000355634.9	c.-180-48254A>G		intron_variant		2		ENSP00000347852	P1

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

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.664

Alfa AF: 0.666 Hom.: 44958

Bravo AF: 0.657

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13132552; hg19: chr4-186744774;