2-113640930-C-G

Variant names:

• chr2-113640930-C-G
• rs780172866
• NM_001306158.2:c.334C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001306158.2(RABL2A):​c.334C>G​(p.Leu112Val) 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. 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. L112M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RABL2A NM_001306158.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 0 publications found

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]

RPL23AP7 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38005486).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306158.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL2A	NM_001306158.2	MANE Select	c.334C>G	p.Leu112Val	missense	Exon 6 of 9	NP_001293087.1	Q9UBK7-2
	RABL2A	NM_001354405.2		c.334C>G	p.Leu112Val	missense	Exon 7 of 10	NP_001341334.1
	RABL2A	NM_001354406.2		c.334C>G	p.Leu112Val	missense	Exon 6 of 9	NP_001341335.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL2A	ENST00000683472.1	MANE Select	c.334C>G	p.Leu112Val	missense	Exon 6 of 9	ENSP00000507832.1	Q9UBK7-2
	RABL2A	ENST00000409875.5	TSL:1	c.334C>G	p.Leu112Val	missense	Exon 7 of 10	ENSP00000387229.1	Q9UBK7-3
	RABL2A	ENST00000393165.7	TSL:1	c.334C>G	p.Leu112Val	missense	Exon 6 of 10	ENSP00000376870.3	Q9UBK7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.91	L
PhyloP100		-0.013
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.43
Sift	Benign	0.13	T
Sift4G	Benign	0.21	T
Polyphen		0.98	D
Vest4		0.59
MutPred		0.47		Gain of MoRF binding (P = 0.084)
MVP		0.68
MPC		3.0
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.45
gMVP		0.71
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs780172866; hg19: chr2-114398507;