5-81201393-G-C

Variant names:

• chr5-81201393-G-C
• NM_006909.3:c.2857G>C

Variant summary

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

The NM_006909.3(RASGRF2):​c.2857G>C​(p.Asp953His) 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: RASGRF2 NM_006909.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.14
• Publications: 0 publications found

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

CKMT2-AS1 (HGNC:48997): (CKMT2 antisense RNA 1)

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_006909.3. 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
	RASGRF2	NM_006909.3	MANE Select	c.2857G>C	p.Asp953His	missense	Exon 19 of 27	NP_008840.1	O14827

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	ENST00000265080.9	TSL:1 MANE Select	c.2857G>C	p.Asp953His	missense	Exon 19 of 27	ENSP00000265080.4	O14827
	RASGRF2	ENST00000503795.1	TSL:1	n.2857G>C		non_coding_transcript_exon	Exon 19 of 28	ENSP00000421771.1	D6RAS9
	RASGRF2	ENST00000933988.1		c.2812G>C	p.Asp938His	missense	Exon 19 of 27	ENSP00000604047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.26		Loss of disorder (P = 0.0834)
MVP		0.29
MPC		1.1
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.64
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-80497212; COSMIC: COSV99428282; COSMIC: COSV99428282;