11-106810183-T-C

Position:

• chr11-106810183-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000855.3(GUCY1A2):​c.1502A>G​(p.Asp501Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCY1A2 NM_000855.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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]

ACMG classification

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=0.4034902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.1502A>G	p.Asp501Gly	missense_variant	5/8	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.1502A>G	p.Asp501Gly	missense_variant	5/9		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1502A>G	p.Asp501Gly	missense_variant	5/8	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.1502A>G	p.Asp501Gly	missense_variant	5/9	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.1565A>G	p.Asp522Gly	missense_variant	6/9	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.1502A>G (p.D501G) alteration is located in exon 5 (coding exon 5) of the GUCY1A2 gene. This alteration results from a A to G substitution at nucleotide position 1502, causing the aspartic acid (D) at amino acid position 501 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	0.28
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;.;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	T;D;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		0.82	P;B;.
Vest4		0.44
MutPred		0.59		Gain of catalytic residue at Q504 (P = 0.0465);Gain of catalytic residue at Q504 (P = 0.0465);.;
MVP		0.86
MPC		1.1
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-106680909;