4-185611840-AGG-CGC

Variant names:

• chr4-185611840-AGG-CGC
• NM_001395207.1:c.3622_3624delCCTinsGCG
• SORBS2 p.Pro1208Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001395207.1(SORBS2):​c.3622_3624delCCTinsGCG​(p.Pro1208Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1208T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SORBS2 NM_001395207.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395207.1. 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_001395207.1	MANE Select	c.3622_3624delCCTinsGCG	p.Pro1208Ala	missense	N/A	NP_001382136.1	A0A8Q3WKK4
	SORBS2	NM_001394245.1		c.3580_3582delCCTinsGCG	p.Pro1194Ala	missense	N/A	NP_001381174.1
	SORBS2	NM_001394246.1		c.3523_3525delCCTinsGCG	p.Pro1175Ala	missense	N/A	NP_001381175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	ENST00000695409.1	MANE Select	c.3622_3624delCCTinsGCG	p.Pro1208Ala	missense	N/A	ENSP00000511888.1	A0A8Q3WKK4
	SORBS2	ENST00000284776.11	TSL:1	c.3022_3024delCCTinsGCG	p.Pro1008Ala	missense	N/A	ENSP00000284776.7	O94875-1
	SORBS2	ENST00000437304.6	TSL:1	c.2194_2196delCCTinsGCG	p.Pro732Ala	missense	N/A	ENSP00000396008.2	O94875-10

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-186532994;