2-113640946-C-A

Variant names:

• chr2-113640946-C-A
• NM_001306158.2:c.350C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001306158.2(RABL2A):​c.350C>A​(p.Thr117Lys) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RABL2A NM_001306158.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.0390957).

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.350C>A	p.Thr117Lys	missense	Exon 6 of 9	NP_001293087.1	Q9UBK7-2
	RABL2A	NM_001354405.2		c.350C>A	p.Thr117Lys	missense	Exon 7 of 10	NP_001341334.1
	RABL2A	NM_001354406.2		c.350C>A	p.Thr117Lys	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.350C>A	p.Thr117Lys	missense	Exon 6 of 9	ENSP00000507832.1	Q9UBK7-2
	RABL2A	ENST00000409875.5	TSL:1	c.350C>A	p.Thr117Lys	missense	Exon 7 of 10	ENSP00000387229.1	Q9UBK7-3
	RABL2A	ENST00000393165.7	TSL:1	c.350C>A	p.Thr117Lys	missense	Exon 6 of 10	ENSP00000376870.3	Q9UBK7-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000342 AC: 5 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 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: 53418

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 29

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	Benign	0.077
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.0
DANN	Benign	0.14
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.3	N
PhyloP100		2.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.43		Gain of ubiquitination at T117 (P = 0.023)
MVP		0.30
MPC		1.9
ClinPred		0.028	T
GERP RS		1.0
Varity_R		0.029
gMVP		0.61
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr2-114398523;