Variant 4-7992867-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130083.2(ABLIM2):c.1679G>A(p.Arg560Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,612,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ABLIM2
NM_001130083.2 missense, splice_region

Scores

Splicing: ADA: 0.0009687

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

ABLIM2 (HGNC:19195): (actin binding LIM protein family member 2) Predicted to enable actin filament binding activity. Predicted to be involved in lamellipodium assembly. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ABLIM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04199779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM2	NM_001130083.2 linkuse as main transcript	c.1679G>A	p.Arg560Gln	missense_variant, splice_region_variant	17/21	ENST00000447017.7	NP_001123555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABLIM2	ENST00000447017.7 linkuse as main transcript	c.1679G>A	p.Arg560Gln	missense_variant, splice_region_variant	17/21	1	NM_001130083.2	ENSP00000393511	P4	Q6H8Q1-9

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000244

AC:

AN:

246402

Hom.:

AF XY:

0.000224

AC XY:

AN XY:

133904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000496

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000155

AC:

226

AN:

1460140

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000539

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000171

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000178

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 01, 2022

The c.1679G>A (p.R560Q) alteration is located in exon 17 (coding exon 17) of the ABLIM2 gene. This alteration results from a G to A substitution at nucleotide position 1679, causing the arginine (R) at amino acid position 560 to be replaced by a glutamine (Q). 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

Benign

0.077

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

.;.;T;T;.

Eigen

Benign

0.042

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.81

T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

.;.;L;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D;D;D;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.75

N;N;N;.;N

REVEL

Benign

0.086

Sift

Benign

0.56

T;T;T;.;T

Sift4G

Benign

0.53

T;T;T;T;T

Polyphen

1.0

D;.;P;.;.

Vest4

0.13

MVP

0.58

MPC

0.056

ClinPred

0.031

GERP RS

3.8

Varity_R

0.065

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00097

dbscSNV1_RF

Benign

0.048

SpliceAI score (max)

0.010

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