Genetic Variant ABLIM2:p.Val619Glu (chr4-7967072-A-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001130083.2(ABLIM2):c.1856T>A(p.Val619Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V619A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ABLIM2
NM_001130083.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.48

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

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.1856T>A	p.Val619Glu	missense	Exon 21 of 21	NP_001123555.1	A0A140VK02
ABLIM2	NM_001130084.2		c.1754T>A	p.Val585Glu	missense	Exon 20 of 20	NP_001123556.1	Q6H8Q1-1
ABLIM2	NM_001130085.2		c.1637T>A	p.Val546Glu	missense	Exon 18 of 18	NP_001123557.1	Q6H8Q1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABLIM2	ENST00000447017.7	TSL:1 MANE Select	c.1856T>A	p.Val619Glu	missense	Exon 21 of 21	ENSP00000393511.2	Q6H8Q1-9
ABLIM2	ENST00000341937.9	TSL:1	c.1754T>A	p.Val585Glu	missense	Exon 20 of 20	ENSP00000342813.5	Q6H8Q1-1
ABLIM2	ENST00000361581.9	TSL:1	c.1637T>A	p.Val546Glu	missense	Exon 18 of 18	ENSP00000355003.5	Q6H8Q1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461542

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111888

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

-0.050

MutationAssessor

Pathogenic

3.7

PhyloP100

8.5

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.98

Vest4

0.84

MutPred

0.66

Gain of disorder (P = 0.0014)

MVP

0.48

MPC

0.41

ClinPred

0.99

GERP RS

4.5

Varity_R

0.91

gMVP

0.76

Mutation Taster

=33/67

disease causing

(source)

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

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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