rs12449814

Positions:

• chr17-8008391-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254854.5(GUCY2D):​c.1668+359G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 152,258 control chromosomes in the GnomAD database, including 200 homozygotes. 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: 𝑓 0.040 (200 hom., cov: 32)
• Consequence: GUCY2D ENST00000254854.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

GUCY2D (HGNC:4689): (guanylate cyclase 2D, retinal) This gene encodes a retina-specific guanylate cyclase, which is a member of the membrane guanylyl cyclase family. Like other membrane guanylyl cyclases, this enzyme has a hydrophobic amino-terminal signal sequence followed by a large extracellular domain, a single membrane spanning domain, a kinase homology domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane guanylyl cyclases, this enzyme is not activated by natriuretic peptides. Mutations in this gene result in Leber congenital amaurosis and cone-rod dystrophy-6 diseases. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY2D	NM_000180.4	c.1668+359G>T		intron_variant		ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2	c.1668+359G>T		intron_variant			XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5	c.1668+359G>T		intron_variant		1	NM_000180.4	ENSP00000254854	P1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6022 AN: 152140 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0396 AC: 6036 AN: 152258 Hom.: 200 Cov.: 32 AF XY: 0.0402 AC XY: 2995 AN XY: 74460

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0467

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0392 Hom.: 72

Bravo AF: 0.0459

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs12449814; hg19: chr17-7911709;