11-107017827-TGGCCCCGGCAGTGGCAGCGGC-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000855.3(GUCY1A2):c.208_228del(p.Ala70_Ala76del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000867 in 1,153,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: GUCY1A2 NM_000855.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000855.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.208_228del	p.Ala70_Ala76del	inframe_deletion	1/8	ENST00000526355.7
GUCY1A2	NM_001256424.2	c.208_228del	p.Ala70_Ala76del	inframe_deletion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.208_228del	p.Ala70_Ala76del	inframe_deletion	1/8	1	NM_000855.3	P1
GUCY1A2	ENST00000282249.6	c.208_228del	p.Ala70_Ala76del	inframe_deletion	1/9	1
GUCY1A2	ENST00000347596.2	c.208_228del	p.Ala70_Ala76del	inframe_deletion	1/9	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.67e-7 AC: 1 AN: 1153954 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 556884

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: 0.0000334

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Feb 12, 2024

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr11-106888553;