chr11-106776446-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000855.3(GUCY1A2):c.1829C>A(p.Pro610Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,412 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: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
GUCY1A2
NM_000855.3 missense
NM_000855.3 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 6.49
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]
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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=0.41547436).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GUCY1A2 | NM_000855.3 | c.1829C>A | p.Pro610Gln | missense_variant | 6/8 | ENST00000526355.7 | |
LOC112268081 | XR_002957264.2 | n.485+272G>T | intron_variant, non_coding_transcript_variant | ||||
GUCY1A2 | NM_001256424.2 | c.1829C>A | p.Pro610Gln | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GUCY1A2 | ENST00000526355.7 | c.1829C>A | p.Pro610Gln | missense_variant | 6/8 | 1 | NM_000855.3 | P1 | |
GUCY1A2 | ENST00000282249.6 | c.1829C>A | p.Pro610Gln | missense_variant | 6/9 | 1 | |||
GUCY1A2 | ENST00000347596.2 | c.1892C>A | p.Pro631Gln | missense_variant | 7/9 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250822Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135558
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460412Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726610
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
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 submitter | clinical testing | Ambry Genetics | Jan 06, 2023 | The c.1829C>A (p.P610Q) alteration is located in exon 6 (coding exon 6) of the GUCY1A2 gene. This alteration results from a C to A substitution at nucleotide position 1829, causing the proline (P) at amino acid position 610 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0671);Gain of MoRF binding (P = 0.0671);.;
MVP
MPC
0.66
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at