Genetic Variant ABLIM2:p.Gly568Glu (chr4-7984871-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130083.2(ABLIM2):c.1703G>A(p.Gly568Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ABLIM2
NM_001130083.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10641816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130083.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABLIM2	NM_001130083.2	MANE Select	c.1703G>A	p.Gly568Glu	missense	Exon 18 of 21	NP_001123555.1	A0A140VK02
ABLIM2	NM_001130084.2		c.1601G>A	p.Gly534Glu	missense	Exon 17 of 20	NP_001123556.1	Q6H8Q1-1
ABLIM2	NM_001130086.2		c.1445G>A	p.Gly482Glu	missense	Exon 15 of 18	NP_001123558.1	Q6H8Q1-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABLIM2	ENST00000447017.7	TSL:1 MANE Select	c.1703G>A	p.Gly568Glu	missense	Exon 18 of 21	ENSP00000393511.2	Q6H8Q1-9
ABLIM2	ENST00000341937.9	TSL:1	c.1601G>A	p.Gly534Glu	missense	Exon 17 of 20	ENSP00000342813.5	Q6H8Q1-1
ABLIM2	ENST00000361581.9	TSL:1	c.1517-1317G>A		intron	N/A	ENSP00000355003.5	Q6H8Q1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000419

AC:

AN:

238774

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.0000454

AC:

AN:

44008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

84594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109832

Other (OTH)

AF:

0.0000166

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.85

M_CAP

Benign

0.0043

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

PhyloP100

2.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

REVEL

Benign

0.059

Sift

Benign

0.21

Sift4G

Benign

0.44

Polyphen

0.015

Vest4

0.18

MutPred

0.46

Loss of catalytic residue at A535 (P = 0.0612)

MVP

0.11

MPC

0.068

ClinPred

0.29

GERP RS

3.4

Varity_R

0.080

gMVP

0.29

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over