NM_000180.4:c.*143T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 25 publications found

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]

GUCY2D Gene-Disease associations (from GenCC):

• cone-rod dystrophy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• GUCY2D-related dominant retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• GUCY2D-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• night blindness, congenital stationary, type1i

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• central areolar choroidal dystrophy

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000180.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2D	NM_000180.4	MANE Select	c.*143T>C		3_prime_UTR	Exon 20 of 20	NP_000171.1	Q02846

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2D	ENST00000254854.5	TSL:1 MANE Select	c.*143T>C		3_prime_UTR	Exon 20 of 20	ENSP00000254854.4	Q02846

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

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.489 AC: 43 AN: 88

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.915 AC: 37851 AN: 41354

American (AMR) AF: 0.689 AC: 10514 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2015 AN: 3460

East Asian (EAS) AF: 0.944 AC: 4855 AN: 5142

South Asian (SAS) AF: 0.788 AC: 3777 AN: 4794

European-Finnish (FIN) AF: 0.630 AC: 6620 AN: 10514

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34797 AN: 67826

Other (OTH) AF: 0.632 AC: 1335 AN: 2112

Alfa AF: 0.555 Hom.: 66669

Bravo AF: 0.687

Asia WGS AF: 0.889 AC: 3093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.34
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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