Variant 2-203328552-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001375670.1(ABI2):c.38C>T(p.Pro13Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 7.12

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABI2	NM_001375670.1 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/12	ENST00000261018.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABI2	ENST00000261018.12 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/12	1	NM_001375670.1
	ENST00000469747.2 linkuse as main transcript	n.405-71G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000844

AC:

AN:

237030

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129314

show subpopulations

Gnomad AFR exome

AF:

0.0000714

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:

0.00000940

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722848

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 09, 2024

The c.38C>T (p.P13L) alteration is located in exon 1 (coding exon 1) of the ABI2 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the proline (P) at amino acid position 13 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

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.55

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

Eigen

Benign

0.039

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.65

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.82

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

MetaSVM

Uncertain

0.41

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-8.0

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

REVEL

Uncertain

0.57

Sift

Uncertain

0.016

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

Sift4G

Uncertain

0.031

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

Polyphen

0.075

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

Vest4

0.57

MutPred

0.46

Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);Loss of disorder (P = 0.0452);

MVP

0.89

MPC

1.3

ClinPred

0.97

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.98

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