1-178727615-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152663.5(RALGPS2):c.-84+2196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,010 control chromosomes in the GnomAD database, including 25,850 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25850 hom., cov: 33)
• Consequence: RALGPS2 NM_152663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALGPS2	NM_152663.5	c.-84+2196T>C		intron_variant		ENST00000367635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALGPS2	ENST00000367635.8	c.-84+2196T>C		intron_variant		1	NM_152663.5	P3
RALGPS2	ENST00000324778.5	c.-84+2196T>C		intron_variant		5
RALGPS2	ENST00000367634.7	c.-84+2196T>C		intron_variant		2		A1
RALGPS2	ENST00000495034.5	n.255+2196T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87700 AN: 151892 Hom.: 25809 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87786 AN: 152010 Hom.: 25850 Cov.: 33 AF XY: 0.581 AC XY: 43196 AN XY: 74314

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.607

Alfa AF: 0.590 Hom.: 33862

Bravo AF: 0.587

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.53

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: rs2773080; hg19: chr1-178696750;