chr5-81070498-G-A

Position:

• chr5-81070498-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000265080.9(RASGRF2):​c.550G>A​(p.Ala184Thr) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASGRF2 ENST00000265080.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24854445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.550G>A	p.Ala184Thr	missense_variant	4/27	ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.550G>A	p.Ala184Thr	missense_variant	4/27	1	NM_006909.3	ENSP00000265080	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1446946 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 14, 2023

The c.550G>A (p.A184T) alteration is located in exon 1 (coding exon 1) of the RASGRF2 gene. This alteration results from a G to A substitution at nucleotide position 550, causing the alanine (A) at amino acid position 184 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.18
Sift	Benign	0.089	T;.
Sift4G	Benign	0.17	T;.
Polyphen		0.098	B;.
Vest4		0.34
MutPred		0.21		Gain of phosphorylation at A184 (P = 0.03);Gain of phosphorylation at A184 (P = 0.03);
MVP		0.16
MPC		1.3
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.20
gMVP		0.39

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: chr5-80366317;