5-80960751-G-T

Variant names:

• chr5-80960751-G-T
• rs759262766
• NM_006909.3:c.13G>T

Variant summary

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

The NM_006909.3(RASGRF2):​c.13G>T​(p.Val5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,443,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RASGRF2 NM_006909.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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]

RASGRF2-AS1 (HGNC:40499): (RASGRF2 antisense RNA 1)

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 rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 27	ENST00000265080.9	NP_008840.1
RASGRF2	XM_005248565.2	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 19		XP_005248622.1
RASGRF2	XM_017009683.2	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 18		XP_016865172.1
RASGRF2-AS1	NR_105015.1	n.127+30C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 27	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.13G>T		non_coding_transcript_exon_variant	Exon 1 of 28	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 10	5		ENSP00000491428.1
RASGRF2-AS1	ENST00000505694.1	n.127+30C>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1443872 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 715896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000513

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Uncertain	0.039	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.1	N;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.019	D;.
Polyphen		0.96	P;.
Vest4		0.33
MutPred		0.26		Loss of methylation at K3 (P = 0.0508);Loss of methylation at K3 (P = 0.0508);
MVP		0.63
MPC		1.9
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.46
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs759262766; hg19: chr5-80256570;