4-8009080-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130083.2(ABLIM2):c.1446G>T(p.Glu482Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 (0 hom.)
• Consequence: ABLIM2 NM_001130083.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.379

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21571851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABLIM2	NM_001130083.2	c.1446G>T	p.Glu482Asp	missense_variant	15/21	ENST00000447017.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABLIM2	ENST00000447017.7	c.1446G>T	p.Glu482Asp	missense_variant	15/21	1	NM_001130083.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1446G>T (p.E482D) alteration is located in exon 15 (coding exon 15) of the ABLIM2 gene. This alteration results from a G to T substitution at nucleotide position 1446, causing the glutamic acid (E) at amino acid position 482 to be replaced by an aspartic acid (D). 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	0.087
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Uncertain	0.98
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.50	D;D;D;D;D;D;D;N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;.;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.21	T;T;T;T;T;T;.;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0030	B;B;.;B;B;.;.;.;B;.
Vest4		0.32
MutPred		0.33		.;.;.;Gain of glycosylation at S446 (P = 0.0048);Gain of glycosylation at S446 (P = 0.0048);.;.;.;.;.;
MVP		0.65
MPC		0.082
ClinPred		0.94	D
GERP RS		2.0
Varity_R		0.065
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1311703718; hg19: chr4-8010807;