Variant chr11-106939999-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000855.3(GUCY1A2):c.667C>T(p.Pro223Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,822 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: 0.0000034 ( 0 hom. )

Consequence

GUCY1A2
NM_000855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3105666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY1A2	NM_000855.3 linkuse as main transcript	c.667C>T	p.Pro223Ser	missense_variant	4/8	ENST00000526355.7	NP_000846.1	P33402-1
GUCY1A2	NM_001256424.2 linkuse as main transcript	c.667C>T	p.Pro223Ser	missense_variant	4/9		NP_001243353.1	P33402-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GUCY1A2	ENST00000526355.7 linkuse as main transcript	c.667C>T	p.Pro223Ser	missense_variant	4/8	1	NM_000855.3	ENSP00000431245.2	P33402-1
GUCY1A2	ENST00000282249.6 linkuse as main transcript	c.667C>T	p.Pro223Ser	missense_variant	4/9	1		ENSP00000282249.2	P33402-2
GUCY1A2	ENST00000347596.2 linkuse as main transcript	c.667C>T	p.Pro223Ser	missense_variant	4/9	1		ENSP00000344874.2	P33402-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000613

Hom.:

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

Jun 16, 2022

The c.667C>T (p.P223S) alteration is located in exon 4 (coding exon 4) of the GUCY1A2 gene. This alteration results from a C to T substitution at nucleotide position 667, causing the proline (P) at amino acid position 223 to be replaced by a serine (S). 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

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;.

Eigen

Benign

-0.0066

Eigen_PC

Benign

0.092

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.056

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Uncertain

-0.065

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

N;N;N

REVEL

Uncertain

0.55

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.33

MVP

0.79

MPC

0.54

ClinPred

0.56

GERP RS

4.1

Varity_R

0.058

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over