Variant chr16-53434628-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005611.4(RBL2):c.72G>T(p.Glu24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,563,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RBL2
NM_005611.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.995

Variant links:

Genes affected

RBL2 (HGNC:9894): (RB transcriptional corepressor like 2) Enables promoter-specific chromatin binding activity. Involved in regulation of lipid kinase activity. Acts upstream of or within negative regulation of gene expression. Located in chromosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

RBL2 links:

RBL2 (HGNC:):

RBL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17556247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL2	NM_005611.4 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	1/22	ENST00000262133.11	NP_005602.3	Q08999-1
RBL2	NM_001323608.2 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	1/23		NP_001310537.1	Q08999-1
RBL2	NM_001323609.2 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	1/21		NP_001310538.1
RBL2	NM_001323610.2 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	1/22		NP_001310539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBL2	ENST00000262133.11 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	1/22	1	NM_005611.4	ENSP00000262133.6	Q08999-1
RBL2	ENST00000567964.6 linkuse as main transcript	c.-154+352G>T		intron_variant		5		ENSP00000462464.1	J3KSF7
RBL2	ENST00000680543.1 linkuse as main transcript	n.211G>T		non_coding_transcript_exon_variant	1/21

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000719

AC:

AN:

166918

Hom.:

AF XY:

0.0000537

AC XY:

AN XY:

93084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000732

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000312

AC:

AN:

1411418

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

699650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000511

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000374

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151828

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000618

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.72G>T (p.E24D) alteration is located in exon 1 (coding exon 1) of the RBL2 gene. This alteration results from a G to T substitution at nucleotide position 72, causing the glutamic acid (E) at amino acid position 24 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.033

Eigen

Benign

0.15

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.18

MetaSVM

Uncertain

-0.042

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.42

REVEL

Uncertain

0.40

Sift

Benign

0.29

Sift4G

Uncertain

0.056

Polyphen

0.93

Vest4

0.25

MutPred

0.14

Loss of helix (P = 0.028);

MVP

0.71

MPC

0.20

ClinPred

0.22

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.24

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over