2-46576100-G-A

Variant summary

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

The NM_012249.4(RHOQ):​c.215G>A​(p.Arg72His) variant causes a missense change. The variant allele was found at a frequency of 0.00000757 in 1,453,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

RHOQ
NM_012249.4 missense

Scores

6
11
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.88
Variant links:
Genes affected
RHOQ (HGNC:17736): (ras homolog family member Q) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The encoded protein is an important signalling protein for sarcomere assembly and has been shown to play a significant role in the exocytosis of the solute carrier family 2, facilitated glucose transporter member 4 and other proteins, possibly acting as the signal that turns on the membrane fusion machinery. Three related pseudogene have been identified on chromosomes 2 and 14. [provided by RefSeq, Aug 2011]
RHOQ-AS1 (HGNC:40816): (RHOQ antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
RHOQNM_012249.4 linkuse as main transcriptc.215G>A p.Arg72His missense_variant 3/5 ENST00000238738.9 NP_036381.2
RHOQ-AS1NR_104182.1 linkuse as main transcriptn.204+3935C>T intron_variant, non_coding_transcript_variant
RHOQXM_011532726.3 linkuse as main transcriptc.215G>A p.Arg72His missense_variant 3/6 XP_011531028.1
RHOQXM_005264229.3 linkuse as main transcriptc.202-4828G>A intron_variant XP_005264286.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHOQENST00000238738.9 linkuse as main transcriptc.215G>A p.Arg72His missense_variant 3/51 NM_012249.4 ENSP00000238738 P1
RHOQ-AS1ENST00000506009.2 linkuse as main transcriptn.204+3935C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000820
AC:
2
AN:
244034
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132538
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000570
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000900
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000757
AC:
11
AN:
1453318
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
723626
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000238
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023The c.215G>A (p.R72H) alteration is located in exon 3 (coding exon 3) of the RHOQ gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.71
D
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.77
T
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Uncertain
0.19
D
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.6
D
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.014
D
Polyphen
0.80
P
Vest4
0.59
MutPred
0.65
Gain of disorder (P = 0.1364);
MVP
0.95
MPC
1.2
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.85
gMVP
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs950200523; hg19: chr2-46803239; API