2-120286070-C-G

Variant names:

• chr2-120286070-C-G
• NM_002881.3:c.311C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002881.3(RALB):​c.311C>G​(p.Thr104Ser) variant causes a missense change. 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: 6.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002881.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALB	NM_002881.3	MANE Select	c.311C>G	p.Thr104Ser	missense	Exon 3 of 5	NP_002872.1	P11234-1
	RALB	NM_001369400.1		c.311C>G	p.Thr104Ser	missense	Exon 3 of 5	NP_001356329.1	P11234-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALB	ENST00000272519.10	TSL:1 MANE Select	c.311C>G	p.Thr104Ser	missense	Exon 3 of 5	ENSP00000272519.4	P11234-1
	RALB	ENST00000420510.5	TSL:2	c.311C>G	p.Thr104Ser	missense	Exon 3 of 5	ENSP00000414224.1	P11234-1
	RALB	ENST00000862911.1		c.311C>G	p.Thr104Ser	missense	Exon 3 of 5	ENSP00000532970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.72	N
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.38
Sift	Benign	0.064	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.60
MutPred		0.51		Gain of disorder (P = 0.0455)
MVP		0.85
MPC		0.84
ClinPred		0.91	D
GERP RS		6.1
Varity_R		0.76
gMVP		0.53
Mutation Taster		=36/64	disease causing

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

Other links and lift over

hg19: chr2-121043646;