2-113640930-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001306158.2(RABL2A):​c.334C>A​(p.Leu112Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RABL2A NM_001306158.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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>A	p.Leu112Met	missense	Exon 6 of 9	NP_001293087.1	Q9UBK7-2
	RABL2A	NM_001354405.2		c.334C>A	p.Leu112Met	missense	Exon 7 of 10	NP_001341334.1
	RABL2A	NM_001354406.2		c.334C>A	p.Leu112Met	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>A	p.Leu112Met	missense	Exon 6 of 9	ENSP00000507832.1	Q9UBK7-2
	RABL2A	ENST00000409875.5	TSL:1	c.334C>A	p.Leu112Met	missense	Exon 7 of 10	ENSP00000387229.1	Q9UBK7-3
	RABL2A	ENST00000393165.7	TSL:1	c.334C>A	p.Leu112Met	missense	Exon 6 of 10	ENSP00000376870.3	Q9UBK7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461658 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727140

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111828

Other (OTH) AF: 0.0000662 AC: 4 AN: 60378

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.013
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.64
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.56		Gain of MoRF binding (P = 0.0678)
MVP		0.76
MPC		2.9
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.57
gMVP		0.64
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs780172866; hg19: chr2-114398507;