chr2-120286007-T-A

Position:

• chr2-120286007-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002881.3(RALB):​c.248T>A​(p.Phe83Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALB NM_002881.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

RALB (HGNC:9840): (RAS like proto-oncogene B) This gene encodes a GTP-binding protein that belongs to the small GTPase superfamily and Ras family of proteins. GTP-binding proteins mediate the transmembrane signaling initiated by the occupancy of certain cell surface receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALB	NM_002881.3	c.248T>A	p.Phe83Tyr	missense_variant	3/5	ENST00000272519.10	NP_002872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALB	ENST00000272519.10	c.248T>A	p.Phe83Tyr	missense_variant	3/5	1	NM_002881.3	ENSP00000272519.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 15, 2024

The c.248T>A (p.F83Y) alteration is located in exon 3 (coding exon 2) of the RALB gene. This alteration results from a T to A substitution at nucleotide position 248, causing the phenylalanine (F) at amino acid position 83 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T;T;T
Eigen	Benign	-0.044
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-1.1	.;N;N;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.81	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.25	T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.0070	.;B;B;.;.
Vest4		0.71, 0.67
MutPred		0.67		.;Loss of stability (P = 0.1007);Loss of stability (P = 0.1007);Loss of stability (P = 0.1007);Loss of stability (P = 0.1007);
MVP		0.77
MPC		1.2
ClinPred		0.92	D
GERP RS		6.0
Varity_R		0.40
gMVP		0.83

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: chr2-121043583;