17-81868598-AAAGGGCAGCAGAGGCCTGGCTGCGGCCTCTCTCCCCCACAGCACAGGCAGAAGCAGCAACGAGACAGGAGACCGAGGAGGCTGGGCCTGTGGGTGGGGGAGGGCTGAGGAGGGGGGTCGGAGGCACTCGGTTGAGCCAGGCCAGGGAGGCGGACCAGGGTGGGAGGGGCACGGAGGGCCTGTCAGCACTTTGGTATGGGGAGGGGAGGGGCTGGGGGGGACACATCCGCCTGTCCGTCGTCCGTCCGTCAGTCTGCCCTGCCCGCCTCTGGCTGGGCTCAGTCCTTCCAGTCCTTCTTGATGGTGAGATTCCACTCCCAGGACAGGTGGTCGGTCTTGTCGTCGTCTGTGAAGCGGGACTTGATGCTGTAGCTGCCCCGGGCCAGCATACCCTTGGGTGCCTCCTCCACGGGGGTCAGGAACTCGTACTCCTCGG-CACAGGCAGAAGCAGCAACGAGACAGGAGA

Position:

• chr17-81868598-AAAGGGCAGCAGAGGCCTGGCTGCGGCCTCTCTCCCCCACAGCACAGGCAGAAGCAGCAACGAGACAGGAGACCGAGGAGGCTGGGCCTGTGGGTGGGGGAGGGCTGAGGAGGGGGGTCGGAGGCACTCGGTTGAGCCAGGCCAGGGAGGCGGACCAGGGTGGGAGGGGCACGGAGGGCCTGTCAGCACTTTGGTATGGGGAGGGGAGGGGCTGGGGGGGACACATCCGCCTGTCCGTCGTCCGTCCGTCAGTCTGCCCTGCCCGCCTCTGGCTGGGCTCAGTCCTTCCAGTCCTTCTTGATGGTGAGATTCCACTCCCAGGACAGGTGGTCGGTCTTGTCGTCGTCTGTGAAGCGGGACTTGATGCTGTAGCTGCCCCGGGCCAGCATACCCTTGGGTGCCTCCTCCACGGGGGTCAGGAACTCGTACTCCTCGG-CACAGGCAGAAGCAGCAACGAGACAGGAGA

Variant summary

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

The NM_001301242.2(ARHGDIA):​c.435+23_781delCCGAGGAGTACGAGTTCCTGACCCCCGTGGAGGAGGCACCCAAGGGTATGCTGGCCCGGGGCAGCTACAGCATCAAGTCCCGCTTCACAGACGACGACAAGACCGACCACCTGTCCTGGGAGTGGAATCTCACCATCAAGAAGGACTGGAAGGACTGAGCCCAGCCAGAGGCGGGCAGGGCAGACTGACGGACGGACGACGGACAGGCGGATGTGTCCCCCCCAGCCCCTCCCCTCCCCATACCAAAGTGCTGACAGGCCCTCCGTGCCCCTCCCACCCTGGTCCGCCTCCCTGGCCTGGCTCAACCGAGTGCCTCCGACCCCCCTCCTCAGCCCTCCCCCACCCACAGGCCCAGCCTCCTCGGTCTCCTGTCTCGTTGCTGCTTCTGCCTGTGCTGTGGGGGAGAGAGGCCGCAGCCAGGCCTCTGCTGCCCTTTinsTCTCCTGTCTCGTTGCTGCTTCTGCCTGTG​(p.Thr146fs) variant causes a frameshift, splice acceptor, missense, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGDIA NM_001301242.2 frameshift, splice_acceptor, missense, splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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.458_*278delCCGAGGAGTACGAGTTCCTGACCCCCGTGGAGGAGGCACCCAAGGGTATGCTGGCCCGGGGCAGCTACAGCATCAAGTCCCGCTTCACAGACGACGACAAGACCGACCACCTGTCCTGGGAGTGGAATCTCACCATCAAGAAGGACTGGAAGGACTGAGCCCAGCCAGAGGCGGGCAGGGCAGACTGACGGACGGACGACGGACAGGCGGATGTGTCCCCCCCAGCCCCTCCCCTCCCCATACCAAAGTGCTGACAGGCCCTCCGTGCCCCTCCCACCCTGGTCCGCCTCCCTGGCCTGGCTCAACCGAGTGCCTCCGACCCCCCTCCTCAGCCCTCCCCCACCCACAGGCCCAGCCTCCTCGGTCTCCTGTCTCGTTGCTGCTTCTGCCTGTGCTGTGGGGGAGAGAGGCCGCAGCCAGGCCTCTGCTGCCCTTTinsTCTCCTGTCTCGTTGCTGCTTCTGCCTGTG	p.Ala153fs	frameshift_variant, stop_lost, synonymous_variant	6/6	ENST00000269321.12	NP_004300.1
ARHGDIA	NM_004309.6	c.451_*278delCCGAGGAGTACGAGTTCCTGACCCCCGTGGAGGAGGCACCCAAGGGTATGCTGGCCCGGGGCAGCTACAGCATCAAGTCCCGCTTCACAGACGACGACAAGACCGACCACCTGTCCTGGGAGTGGAATCTCACCATCAAGAAGGACTGGAAGGACTGAGCCCAGCCAGAGGCGGGCAGGGCAGACTGACGGACGGACGACGGACAGGCGGATGTGTCCCCCCCAGCCCCTCCCCTCCCCATACCAAAGTGCTGACAGGCCCTCCGTGCCCCTCCCACCCTGGTCCGCCTCCCTGGCCTGGCTCAACCGAGTGCCTCCGACCCCCCTCCTCAGCCCTCCCCCACCCACAGGCCCAGCCTCCTCGGTCTCCTGTCTCGTTGCTGCTTCTGCCTGTGCTGTGGGGGAGAGAGGCCGCAGCCAGGCCTCTGCTGCCCTTTinsTCTCCTGTCTCGTTGCTGCTTCTGCCTGTG		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	ENST00000269321.12	c.458_*278delCCGAGGAGTACGAGTTCCTGACCCCCGTGGAGGAGGCACCCAAGGGTATGCTGGCCCGGGGCAGCTACAGCATCAAGTCCCGCTTCACAGACGACGACAAGACCGACCACCTGTCCTGGGAGTGGAATCTCACCATCAAGAAGGACTGGAAGGACTGAGCCCAGCCAGAGGCGGGCAGGGCAGACTGACGGACGGACGACGGACAGGCGGATGTGTCCCCCCCAGCCCCTCCCCTCCCCATACCAAAGTGCTGACAGGCCCTCCGTGCCCCTCCCACCCTGGTCCGCCTCCCTGGCCTGGCTCAACCGAGTGCCTCCGACCCCCCTCCTCAGCCCTCCCCCACCCACAGGCCCAGCCTCCTCGGTCTCCTGTCTCGTTGCTGCTTCTGCCTGTGCTGTGGGGGAGAGAGGCCGCAGCCAGGCCTCTGCTGCCCTTTinsTCTCCTGTCTCGTTGCTGCTTCTGCCTGTG	p.Ala153fs	frameshift_variant, stop_lost, synonymous_variant	6/6	1	NM_004309.6	ENSP00000269321.7
ARHGDIA	ENST00000269321	c.451_*278delCCGAGGAGTACGAGTTCCTGACCCCCGTGGAGGAGGCACCCAAGGGTATGCTGGCCCGGGGCAGCTACAGCATCAAGTCCCGCTTCACAGACGACGACAAGACCGACCACCTGTCCTGGGAGTGGAATCTCACCATCAAGAAGGACTGGAAGGACTGAGCCCAGCCAGAGGCGGGCAGGGCAGACTGACGGACGGACGACGGACAGGCGGATGTGTCCCCCCCAGCCCCTCCCCTCCCCATACCAAAGTGCTGACAGGCCCTCCGTGCCCCTCCCACCCTGGTCCGCCTCCCTGGCCTGGCTCAACCGAGTGCCTCCGACCCCCCTCCTCAGCCCTCCCCCACCCACAGGCCCAGCCTCCTCGGTCTCCTGTCTCGTTGCTGCTTCTGCCTGTGCTGTGGGGGAGAGAGGCCGCAGCCAGGCCTCTGCTGCCCTTTinsTCTCCTGTCTCGTTGCTGCTTCTGCCTGTG		3_prime_UTR_variant	6/6	1	NM_004309.6	ENSP00000269321.7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 02, 2023

This sequence change results in a frameshift in the ARHGDIA gene (p.Ala153Valfs*88). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the ARHGDIA protein and extend the protein by 35 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ARHGDIA-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr17-79826474;