rs6552924

Variant names:

• chr4-185812749-C-A
• rs6552924
• ENST00000284776.11:c.-337-37383G>T

Variant summary

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

The NM_001394248.1(SORBS2):​c.-172-37383G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,086 control chromosomes in the GnomAD database, including 7,281 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 0.30 (7281 hom., cov: 33)
• Consequence: SORBS2 NM_001394248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394248.1. 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
	SORBS2	NM_001394248.1		c.-172-37383G>T		intron	N/A	NP_001381177.1
	SORBS2	NM_001270771.3		c.-180-37383G>T		intron	N/A	NP_001257700.1	O94875-11
	SORBS2	NM_001394255.1		c.-168-37383G>T		intron	N/A	NP_001381184.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	ENST00000284776.11	TSL:1	c.-337-37383G>T		intron	N/A	ENSP00000284776.7	O94875-1
	SORBS2	ENST00000469627.1	TSL:1	n.154-37383G>T		intron	N/A
	SORBS2	ENST00000865659.1		c.-1262G>T		5_prime_UTR	Exon 1 of 23	ENSP00000535718.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46271 AN: 151966 Hom.: 7279 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.304 AC: 46284 AN: 152086 Hom.: 7281 Cov.: 33 AF XY: 0.304 AC XY: 22583 AN XY: 74330

African (AFR) AF: 0.242 AC: 10025 AN: 41492

American (AMR) AF: 0.305 AC: 4667 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1447 AN: 5180

South Asian (SAS) AF: 0.324 AC: 1552 AN: 4794

European-Finnish (FIN) AF: 0.334 AC: 3531 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23225 AN: 67974

Other (OTH) AF: 0.279 AC: 589 AN: 2110

Alfa AF: 0.327 Hom.: 1329

Bravo AF: 0.301

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.42
PhyloP100		0.17
PromoterAI		-0.015	Neutral
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: rs6552924; hg19: chr4-186733903;