rs757131763

Positions:

• chr17-81868810-TG-T
• chr17-81868810-TG-TGG
• chr17-81868810-TG-TGGGG
• chr17-81868810-TG-TGGGGGG
• chr17-81868810-TG-TGGGGGGGGGGGGGGGTGG

Variant summary

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

The NM_001301242.2(ARHGDIA):​c.568delC​(p.Gln190fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 437,590 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: ARHGDIA NM_001301242.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

Genes affected

ARHGDIA (HGNC:678): (Rho GDP dissociation inhibitor alpha) This gene encodes a protein that plays a key role in the regulation of signaling through Rho GTPases. The encoded protein inhibits the disassociation of Rho family members from GDP (guanine diphosphate), thereby maintaining these factors in an inactive state. Activity of this protein is important in a variety of cellular processes, and expression of this gene may be altered in tumors. Mutations in this gene have been found in individuals with nephrotic syndrome, type 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ARHGDIA (HGNC:):

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/exons	MANE	Protein	UniProt
ARHGDIA	NM_004309.6	c.*65delC		3_prime_UTR_variant	6/6	ENST00000269321.12	NP_004300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGDIA	ENST00000269321	c.*65delC		3_prime_UTR_variant	6/6	1	NM_004309.6	ENSP00000269321.7

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 7 AN: 40934 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000496

Gnomad SAS AF: 0.000740

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000221 AC: 45 AN: 204026 Hom.: 1 AF XY: 0.000249 AC XY: 28 AN XY: 112298

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000309

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.000738

Gnomad SAS exome AF: 0.000743

Gnomad FIN exome AF: 0.0000531

Gnomad NFE exome AF: 0.0000319

Gnomad OTH exome AF: 0.000208

GnomAD4 exome AF: 0.000303 AC: 120 AN: 396596 Hom.: 1 Cov.: 35 AF XY: 0.000365 AC XY: 79 AN XY: 216660

Gnomad4 AFR exome AF: 0.000435

Gnomad4 AMR exome AF: 0.000309

Gnomad4 ASJ exome AF: 0.0000945

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.0000401

Gnomad4 NFE exome AF: 0.000125

Gnomad4 OTH exome AF: 0.000423

GnomAD4 genome AF: 0.000171 AC: 7 AN: 40994 Hom.: 0 Cov.: 32 AF XY: 0.0000494 AC XY: 1 AN XY: 20260

Gnomad4 AFR AF: 0.000473

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000496

Gnomad4 SAS AF: 0.000739

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs757131763; hg19: chr17-79826686;