4-7983304-C-T

Position:

• chr4-7983304-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130083.2(ABLIM2):​c.1784G>A​(p.Arg595His) variant causes a missense change. The variant allele was found at a frequency of 0.0000377 in 1,460,322 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: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ABLIM2 NM_001130083.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

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]

ACMG classification

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, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABLIM2	NM_001130083.2	c.1784G>A	p.Arg595His	missense_variant	20/21	ENST00000447017.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABLIM2	ENST00000447017.7	c.1784G>A	p.Arg595His	missense_variant	20/21	1	NM_001130083.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000203 AC: 5 AN: 246284 Hom.: 0 AF XY: 0.0000374 AC XY: 5 AN XY: 133692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.0000670

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 55 AN: 1460322 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 726196

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000264

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

High myopia Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Pathogenic	1.0
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.74	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationTaster	Benign	0.99	D;D;D;D;D;D;D;D;D;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D;D;.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D;D;D;D;.;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;D;.;.;.
Vest4		0.79
MutPred		0.55		.;.;.;Loss of MoRF binding (P = 0.0266);.;.;.;.;
MVP		0.45
MPC		0.31
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.53
gMVP		0.40

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

Other links and lift over

dbSNP: rs750016618; hg19: chr4-7985031;