4-7984887-T-G

Position:

• chr4-7984887-T-G

Variant summary

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

The NM_001130083.2(ABLIM2):​c.1687A>C​(p.Asn563His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABLIM2 NM_001130083.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

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 (HGNC:):

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=0.18398428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABLIM2	NM_001130083.2	c.1687A>C	p.Asn563His	missense_variant	18/21	ENST00000447017.7	NP_001123555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABLIM2	ENST00000447017.7	c.1687A>C	p.Asn563His	missense_variant	18/21	1	NM_001130083.2	ENSP00000393511.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 07, 2024

The c.1687A>C (p.N563H) alteration is located in exon 18 (coding exon 18) of the ABLIM2 gene. This alteration results from a A to C substitution at nucleotide position 1687, causing the asparagine (N) at amino acid position 563 to be replaced by a histidine (H). 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	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	.;.;T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.021
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	.;.;L;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.2	N;N;N;.;N
REVEL	Benign	0.032
Sift	Uncertain	0.025	D;D;D;.;D
Sift4G	Benign	0.097	T;T;T;T;T
Polyphen		0.028	B;.;B;.;.
Vest4		0.34
MutPred		0.37		.;.;Gain of disorder (P = 0.1723);.;.;
MVP		0.42
MPC		0.14
ClinPred		0.54	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-7986614;