Variant 11-106708543-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000855.3(GUCY1A2):c.1960C>G(p.Arg654Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GUCY1A2
NM_000855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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]

GUCY1A2 links:

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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	UniProt
GUCY1A2	NM_000855.3 linkuse as main transcript	c.1960C>G	p.Arg654Gly	missense_variant	7/8	ENST00000526355.7
GUCY1A2	NM_001256424.2 linkuse as main transcript	c.2053C>G	p.Arg685Gly	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7 linkuse as main transcript	c.1960C>G	p.Arg654Gly	missense_variant	7/8	1	NM_000855.3	P1	P33402-1
GUCY1A2	ENST00000282249.6 linkuse as main transcript	c.2053C>G	p.Arg685Gly	missense_variant	8/9	1			P33402-2
GUCY1A2	ENST00000347596.2 linkuse as main transcript	c.2023C>G	p.Arg675Gly	missense_variant	8/9	1			P33402-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249818

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460476

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726550

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Aug 12, 2021

The c.1960C>G (p.R654G) alteration is located in exon 7 (coding exon 7) of the GUCY1A2 gene. This alteration results from a C to G substitution at nucleotide position 1960, causing the arginine (R) at amino acid position 654 to be replaced by a glycine (G). 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

0.18

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

-0.050

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

-1.7

N;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.063

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.011

B;B;.

Vest4

0.82

MutPred

0.68

Gain of methylation at R655 (P = 0.0669);.;.;

MVP

0.65

MPC

0.73

ClinPred

0.20

GERP RS

5.1

Varity_R

0.25

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over