Variant chr2-203328626-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001375670.1(ABI2):c.112A>T(p.Ile38Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000183 in 1,581,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ABI2
NM_001375670.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

ENSG00000256458 (HGNC:):

ENSG00000256458 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2702944).

BS2

High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI2	NM_001375670.1 link	c.112A>T	p.Ile38Leu	missense_variant	1/12	ENST00000261018.12	NP_001362599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI2	ENST00000261018.12 link	c.112A>T	p.Ile38Leu	missense_variant	1/12	1	NM_001375670.1	ENSP00000261018.9		F8WAL6

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000137

AC:

AN:

219410

Hom.:

AF XY:

0.00000828

AC XY:

AN XY:

120744

show subpopulations

Gnomad AFR exome

AF:

0.0000837

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:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1430240

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

711878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000997

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:

0.0000210

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

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

Dec 10, 2024

The c.112A>T (p.I38L) alteration is located in exon 1 (coding exon 1) of the ABI2 gene. This alteration results from a A to T substitution at nucleotide position 112, causing the isoleucine (I) at amino acid position 38 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

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.13

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

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.91

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

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.27

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

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.10

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

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

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

REVEL

Uncertain

0.30

Sift

Benign

0.36

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

Sift4G

Benign

0.65

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

Polyphen

0.0

.;.;B;.;.;.;.

Vest4

0.16

MutPred

0.33

Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);Loss of methylation at K43 (P = 0.0491);

MVP

0.57

MPC

0.66

ClinPred

0.19

GERP RS

3.8

gMVP

0.85

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