rs1558114586

Variant names:

• chr1-178776805-C-G
• rs1558114586
• NM_152663.5:c.41C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-178776805-C-G
• chr1-178776805-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152663.5(RALGPS2):​c.41C>G​(p.Ala14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RALGPS2 NM_152663.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

Genes affected

RALGPS2 (HGNC:30279): (Ral GEF with PH domain and SH3 binding motif 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of Ral protein signal transduction; regulation of catalytic activity; and small GTPase mediated signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061112493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152663.5. 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
	RALGPS2	NM_152663.5	MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 2 of 20	NP_689876.2
	RALGPS2	NM_001286247.2		c.41C>G	p.Ala14Gly	missense	Exon 2 of 19	NP_001273176.1	Q86X27-3
	RALGPS2	NM_001400042.1		c.41C>G	p.Ala14Gly	missense	Exon 2 of 19	NP_001386971.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGPS2	ENST00000367635.8	TSL:1 MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 2 of 20	ENSP00000356607.3	Q86X27-1
	RALGPS2	ENST00000853433.1		c.41C>G	p.Ala14Gly	missense	Exon 2 of 20	ENSP00000523492.1
	RALGPS2	ENST00000853430.1		c.41C>G	p.Ala14Gly	missense	Exon 2 of 20	ENSP00000523489.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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	Benign	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.019
Sift	Benign	0.086	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.19		Gain of sheet (P = 0.0101)
MVP		0.11
MPC		0.46
ClinPred		0.25	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.46
Mutation Taster		=85/15	polymorphism

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

dbSNP: rs1558114586; hg19: chr1-178745940;