16-53439026-T-A

Position:

• chr16-53439026-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005611.4(RBL2):​c.251T>A​(p.Leu84His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBL2 NM_005611.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.70

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL2	NM_005611.4	c.251T>A	p.Leu84His	missense_variant	2/22	ENST00000262133.11	NP_005602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11	c.251T>A	p.Leu84His	missense_variant	2/22	1	NM_005611.4	ENSP00000262133.6
RBL2	ENST00000544405.6	c.29T>A	p.Leu10His	missense_variant	2/15	2		ENSP00000443744.2
RBL2	ENST00000567964	c.-143T>A		5_prime_UTR_variant	2/6	5		ENSP00000462464.1
RBL2	ENST00000680543.1	n.390T>A		non_coding_transcript_exon_variant	2/21

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.251T>A (p.L84H) alteration is located in exon 2 (coding exon 2) of the RBL2 gene. This alteration results from a T to A substitution at nucleotide position 251, causing the leucine (L) at amino acid position 84 to be replaced by a histidine (H). 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	0.29
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	D;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.74	T;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		1.0	D;.
Vest4		0.77
MutPred		0.49		Gain of disorder (P = 0.036);.;
MVP		0.91
MPC		0.88
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.66
gMVP		0.59

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.

Other links and lift over

hg19: chr16-53472938;