4-185587666-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001395207.1(SORBS2):c.3864C>A(p.Phe1288Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000573 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

SORBS2
NM_001395207.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

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 links:

SORBS2-AS1 (HGNC:41039): (SORBS2 antisense RNA 1)

SORBS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05460164).

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS2	NM_001395207.1 link	c.3864C>A	p.Phe1288Leu	missense_variant	Exon 27 of 27	ENST00000695409.1	NP_001382136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000695409.1 link	c.3864C>A	p.Phe1288Leu	missense_variant	Exon 27 of 27		NM_001395207.1	ENSP00000511888.1		A0A8Q3WKK4

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000280

AC:

AN:

249748

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000487

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000591

AC:

864

AN:

1461150

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

449

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000693

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000401

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000546

Hom.:

Bravo

AF:

0.000427

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3264C>A (p.F1088L) alteration is located in exon 21 (coding exon 17) of the SORBS2 gene. This alteration results from a C to A substitution at nucleotide position 3264, causing the phenylalanine (F) at amino acid position 1088 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;.;.;T;.;.;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.055

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.44

.;.;.;N;.;.;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.2

.;N;N;N;N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.34

.;T;T;T;T;T;T;T;T

Sift4G

Benign

0.67

.;T;T;T;T;T;T;T;T

Polyphen

0.99, 0.98

.;.;.;D;.;.;.;.;D

Vest4

0.11, 0.12, 0.12, 0.12, 0.13, 0.11

MutPred

0.30

.;.;.;Gain of MoRF binding (P = 0.1294);.;.;.;.;.;

MVP

0.35

MPC

0.29

ClinPred

0.33

GERP RS

3.7

Varity_R

0.24

gMVP

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over