Variant 2-203395741-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001375670.1(ABI2):c.811A>G(p.Ile271Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,824 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: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABI2
NM_001375670.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01

Variant links:

Genes affected

ABI2 (HGNC:24011): (abl interactor 2) Enables several functions, including SH3 domain binding activity; identical protein binding activity; and ubiquitin protein ligase binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of cellular component organization; and zonula adherens assembly. Acts upstream of or within peptidyl-tyrosine phosphorylation. Located in several cellular components, including filopodium tip; lamellipodium; and nucleoplasm. Part of SCAR complex. Is active in adherens junction. Colocalizes with actin filament. [provided by Alliance of Genome Resources, Apr 2022]

ABI2 links:

RAPH1 (HGNC:14436): (Ras association (RalGDS/AF-6) and pleckstrin homology domains 1) This gene encodes a protein that belongs to the Mig10/Rap1-interacting adaptor molecule/Lamellipodin family of adapter proteins, which function in cell migration. Members of this family contain pleckstrin-homology domains, Ras-association domains, and proline-rich C-termini. The protein encoded by this gene regulates actin dynamics through interaction with Ena/Vasodilator proteins as well as direct binding to filamentous actin to regulate actin network assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

RAPH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23389369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABI2	NM_001375670.1 linkuse as main transcript	c.811A>G	p.Ile271Val	missense_variant	7/12	ENST00000261018.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABI2	ENST00000261018.12 linkuse as main transcript	c.811A>G	p.Ile271Val	missense_variant	7/12	1	NM_001375670.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247498

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457824

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.793A>G (p.I265V) alteration is located in exon 6 (coding exon 6) of the ABI2 gene. This alteration results from a A to G substitution at nucleotide position 793, causing the isoleucine (I) at amino acid position 265 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

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

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.64

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

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;.;.;D;T;D;D;D

Sift4G

Benign

0.33

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

Polyphen

0.62, 0.52, 0.14

.;.;P;P;B;.;.;.

Vest4

0.38

MutPred

0.20

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;.;.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.44

MPC

0.73

ClinPred

0.40

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.20

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