chr17-8020246-T-C

Variant names:

• chr17-8020246-T-C
• rs2816
• NM_000180.4:c.*143T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000180.4(GUCY2D):​c.*143T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,772 control chromosomes in the GnomAD database, including 37,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.68 (37034 hom., cov: 28)
  • Exomes 𝑓: 0.52 (18 hom.)
• Consequence: GUCY2D NM_000180.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-8020246-T-C is Benign according to our data. Variant chr17-8020246-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY2D	NM_000180.4	c.*143T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2	c.*3243T>C		3_prime_UTR_variant	Exon 19 of 19		XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5	c.*143T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_000180.4	ENSP00000254854.4

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102274 AN: 151546 Hom.: 36966 Cov.: 28

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.519 AC: 56 AN: 108 Hom.: 18 Cov.: 0 AF XY: 0.560 AC XY: 47 AN XY: 84

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.750

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.675 AC: 102400 AN: 151664 Hom.: 37034 Cov.: 28 AF XY: 0.683 AC XY: 50619 AN XY: 74102

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.632

Alfa AF: 0.546 Hom.: 30907

Bravo AF: 0.687

Asia WGS AF: 0.889 AC: 3093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.34

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: rs2816; hg19: chr17-7923564; COSMIC: COSV54698544; COSMIC: COSV54698544;