dbSNP rs376664304: RABL2A:p.Ser9Asn (chr2-113628632-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001354425.2(RABL2A):c.-253G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RABL2A
NM_001354425.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0680

Publications

0 publications found

Variant links:

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]

RABL2A links:

RPL23AP7 (HGNC:):

RPL23AP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.066202104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354425.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABL2A	NM_001306158.2	MANE Select	c.26G>A	p.Ser9Asn	missense	Exon 2 of 9	NP_001293087.1	Q9UBK7-2
RABL2A	NM_001354425.2		c.-253G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001341354.1
RABL2A	NM_001354426.2		c.-226G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001341355.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RABL2A	ENST00000683472.1	MANE Select	c.26G>A	p.Ser9Asn	missense	Exon 2 of 9	ENSP00000507832.1	Q9UBK7-2
RABL2A	ENST00000409875.5	TSL:1	c.26G>A	p.Ser9Asn	missense	Exon 3 of 10	ENSP00000387229.1	Q9UBK7-3
RABL2A	ENST00000393165.7	TSL:1	c.26G>A	p.Ser9Asn	missense	Exon 2 of 10	ENSP00000376870.3	Q9UBK7-2

Frequencies

GnomAD3 genomes

AF:

0.0000364

AC:

AN:

137380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000197

AC:

AN:

202850

AF XY:

0.00000929

show subpopulations

Gnomad AFR exome

AF:

0.000276

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000714

AC:

AN:

1399692

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

692784

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000247

AC:

AN:

32400

American (AMR)

AF:

0.00

AC:

AN:

42116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23156

East Asian (EAS)

AF:

0.00

AC:

AN:

39192

South Asian (SAS)

AF:

0.00

AC:

AN:

78342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4686

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070158

Other (OTH)

AF:

0.0000172

AC:

AN:

58034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000342383), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000364

AC:

AN:

137380

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

66272

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000147

AC:

AN:

34100

American (AMR)

AF:

0.00

AC:

AN:

13772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

4678

South Asian (SAS)

AF:

0.00

AC:

AN:

3932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9490

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65068

Other (OTH)

AF:

0.00

AC:

AN:

1802

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000328985), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.355

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.1

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.083

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.78

M_CAP

Benign

0.0053

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

PhyloP100

-0.068

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.95

REVEL

Benign

0.11

Sift

Benign

0.42

Sift4G

Benign

0.50

Polyphen

0.011

Vest4

0.20

MVP

0.58

MPC

1.5

ClinPred

0.024

GERP RS

-1.4

Varity_R

0.036

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over