11-106708614-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000855.3(GUCY1A2):​c.1889G>A​(p.Arg630Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,611,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

GUCY1A2
NM_000855.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74
Variant links:
Genes affected
GUCY1A2 (HGNC:4684): (guanylate cyclase 1 soluble subunit alpha 2) Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36733758).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GUCY1A2NM_000855.3 linkc.1889G>A p.Arg630Gln missense_variant Exon 7 of 8 ENST00000526355.7 NP_000846.1 P33402-1
GUCY1A2NM_001256424.2 linkc.1982G>A p.Arg661Gln missense_variant Exon 8 of 9 NP_001243353.1 P33402-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GUCY1A2ENST00000526355.7 linkc.1889G>A p.Arg630Gln missense_variant Exon 7 of 8 1 NM_000855.3 ENSP00000431245.2 P33402-1
GUCY1A2ENST00000282249.6 linkc.1982G>A p.Arg661Gln missense_variant Exon 8 of 9 1 ENSP00000282249.2 P33402-2
GUCY1A2ENST00000347596.2 linkc.1952G>A p.Arg651Gln missense_variant Exon 8 of 9 1 ENSP00000344874.2 P33402-3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151988
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000521
AC:
13
AN:
249674
Hom.:
0
AF XY:
0.0000593
AC XY:
8
AN XY:
135012
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000295
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000230
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1459992
Hom.:
0
Cov.:
30
AF XY:
0.0000523
AC XY:
38
AN XY:
726346
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151988
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000596

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1889G>A (p.R630Q) alteration is located in exon 7 (coding exon 7) of the GUCY1A2 gene. This alteration results from a G to A substitution at nucleotide position 1889, causing the arginine (R) at amino acid position 630 to be replaced by a glutamine (Q). 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
Benign
0.21
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.17
T;.;.
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Uncertain
0.071
D
MutationAssessor
Benign
1.5
L;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Uncertain
0.46
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.010
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.50
MVP
0.87
MPC
0.80
ClinPred
0.24
T
GERP RS
5.9
Varity_R
0.25
gMVP
0.45

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: rs771090233; hg19: chr11-106579340; COSMIC: COSV56507766; API