2-113628611-C-T

Variant names:

• chr2-113628611-C-T
• rs577062989
• NM_001306158.2:c.5C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001306158.2(RABL2A):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000591 in 1,353,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0000059 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RABL2A NM_001306158.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14208552).
• BS2: High AC in GnomAdExome4 at 8 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.5C>T	p.Ala2Val	missense	Exon 2 of 9	NP_001293087.1	Q9UBK7-2
	RABL2A	NM_001354405.2		c.5C>T	p.Ala2Val	missense	Exon 3 of 10	NP_001341334.1
	RABL2A	NM_001354406.2		c.5C>T	p.Ala2Val	missense	Exon 2 of 9	NP_001341335.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL2A	ENST00000683472.1	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 2 of 9	ENSP00000507832.1	Q9UBK7-2
	RABL2A	ENST00000409875.5	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 3 of 10	ENSP00000387229.1	Q9UBK7-3
	RABL2A	ENST00000393165.7	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 2 of 10	ENSP00000376870.3	Q9UBK7-2

Frequencies

GnomAD3 genomes AF: 0.00000718 AC: 1 AN: 139180 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000419 AC: 7 AN: 167146 AF XY: 0.0000457

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000468

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000591 AC: 8 AN: 1353050 Hom.: 0 Cov.: 23 AF XY: 0.00000449 AC XY: 3 AN XY: 668086

African (AFR) AF: 0.00 AC: 0 AN: 31098

American (AMR) AF: 0.00 AC: 0 AN: 36886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21444

East Asian (EAS) AF: 0.000180 AC: 7 AN: 38800

South Asian (SAS) AF: 0.00 AC: 0 AN: 73638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040450

Other (OTH) AF: 0.0000178 AC: 1 AN: 56158

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000718 AC: 1 AN: 139298 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 67236

African (AFR) AF: 0.00 AC: 0 AN: 35176

American (AMR) AF: 0.00 AC: 0 AN: 13944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4762

South Asian (SAS) AF: 0.00 AC: 0 AN: 4040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65404

Other (OTH) AF: 0.00 AC: 0 AN: 1866

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000168 AC: 2

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	0.25
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.98	D
Vest4		0.49
MutPred		0.13		Gain of loop (P = 0.2045)
MVP		0.83
MPC		2.8
ClinPred		0.31	T
GERP RS		2.0
Varity_R		0.17
gMVP		0.64
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs577062989; hg19: chr2-114386188;