Variant 16-53434704-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005611.4(RBL2):c.148G>T(p.Asp50Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,414,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBL2
NM_005611.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37066153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL2	NM_005611.4 linkuse as main transcript	c.148G>T	p.Asp50Tyr	missense_variant	1/22	ENST00000262133.11	NP_005602.3	Q08999-1
RBL2	NM_001323608.2 linkuse as main transcript	c.148G>T	p.Asp50Tyr	missense_variant	1/23		NP_001310537.1	Q08999-1
RBL2	NM_001323609.2 linkuse as main transcript	c.148G>T	p.Asp50Tyr	missense_variant	1/21		NP_001310538.1
RBL2	NM_001323610.2 linkuse as main transcript	c.148G>T	p.Asp50Tyr	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.148G>T	p.Asp50Tyr	missense_variant	1/22	1	NM_005611.4	ENSP00000262133.6	Q08999-1
RBL2	ENST00000567964.6 linkuse as main transcript	c.-154+428G>T		intron_variant		5		ENSP00000462464.1	J3KSF7
RBL2	ENST00000680543.1 linkuse as main transcript	n.287G>T		non_coding_transcript_exon_variant	1/21

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1414094

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2024

The c.148G>T (p.D50Y) 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 148, causing the aspartic acid (D) at amino acid position 50 to be replaced by a tyrosine (Y). 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

0.16

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.11

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.36

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.30

Vest4

0.35

MVP

0.70

MPC

0.65

ClinPred

0.94

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.24

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over