2-113634181-C-G

Variant names:

• chr2-113634181-C-G
• NM_001306158.2:c.166C>G

Variant summary

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

The NM_001306158.2(RABL2A):​c.166C>G​(p.Leu56Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: RABL2A NM_001306158.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

Genes affected

RABL2A (HGNC:9799): (RAB, member of RAS oncogene family like 2A) This gene is a member of the RAB gene family which belongs to the RAS GTPase superfamily. The proteins in the family of RAS-related signaling molecules are small GTP-binding proteins that play important roles in the regulation of exocytotic and endocytotic pathways. This gene maps to the site of an ancestral telomere fusion event and may be a subtelomeric gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

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=0.23307687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABL2A	NM_001306158.2	c.166C>G	p.Leu56Val	missense_variant	Exon 4 of 9	ENST00000683472.1	NP_001293087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABL2A	ENST00000683472.1	c.166C>G	p.Leu56Val	missense_variant	Exon 4 of 9		NM_001306158.2	ENSP00000507832.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166C>G (p.L56V) alteration is located in exon 4 (coding exon 3) of the RABL2A gene. This alteration results from a C to G substitution at nucleotide position 166, causing the leucine (L) at amino acid position 56 to be replaced by a valine (V). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.;.;T;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	.;.;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-1.1	N;.;.;N;N;N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N;N;D;N;N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.20	T;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T
Polyphen		0.74	P;D;.;.;P;.;D
Vest4		0.55
MutPred		0.50		Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);Loss of stability (P = 0.065);
MVP		0.51
MPC		2.7
ClinPred		0.89	D
GERP RS		3.0
Varity_R		0.33
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-114391758;