1-178727615-T-C

Variant names:

• chr1-178727615-T-C
• rs2773080
• NM_152663.5:c.-84+2196T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RALGPS2	NM_152663.5	c.-84+2196T>C		intron_variant	Intron 1 of 19	ENST00000367635.8	NP_689876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALGPS2	ENST00000367635.8	c.-84+2196T>C		intron_variant	Intron 1 of 19	1	NM_152663.5	ENSP00000356607.3
RALGPS2	ENST00000367634.7	c.-84+2196T>C		intron_variant	Intron 1 of 18	2		ENSP00000356606.2
RALGPS2	ENST00000324778.5	c.-84+2196T>C		intron_variant	Intron 1 of 9	5		ENSP00000313613.5
RALGPS2	ENST00000495034.5	n.255+2196T>C		intron_variant	Intron 1 of 9	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

African (AFR) AF: 0.501 AC: 20767 AN: 41452

American (AMR) AF: 0.684 AC: 10449 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2219 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4003 AN: 5180

South Asian (SAS) AF: 0.750 AC: 3611 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5468 AN: 10562

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39238 AN: 67942

Other (OTH) AF: 0.607 AC: 1282 AN: 2112

Alfa AF: 0.589 Hom.: 42935

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs2773080; hg19: chr1-178696750;