Variant rs10772800 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004963.4(GUCY2C):c.2022C>T(p.Ile674=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 1,613,586 control chromosomes in the GnomAD database, including 755,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 57809 hom., cov: 30)

Exomes 𝑓: 0.97 ( 698108 hom. )

Consequence

GUCY2C
NM_004963.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.410

Variant links:

Genes affected

GUCY2C (HGNC:4688): (guanylate cyclase 2C) This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]

GUCY2C links:

C12orf60 (HGNC:):

C12orf60 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 12-14641128-G-A is Benign according to our data. Variant chr12-14641128-G-A is described in ClinVar as [Benign]. Clinvar id is 402916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14641128-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY2C	NM_004963.4 linkuse as main transcript	c.2022C>T	p.Ile674=	synonymous_variant	18/27	ENST00000261170.5	NP_004954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5 linkuse as main transcript	c.2022C>T	p.Ile674=	synonymous_variant	18/27	1	NM_004963.4	ENSP00000261170	P1

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128078

AN:

151976

Hom.:

57806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.976

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.966

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.977

Gnomad FIN

AF:

0.988

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.880

GnomAD3 exomes

AF:

0.950

AC:

238744

AN:

251312

Hom.:

115493

AF XY:

0.960

AC XY:

130356

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.973

Gnomad ASJ exome

AF:

0.970

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.980

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.970

GnomAD4 exome

AF:

0.974

AC:

1423538

AN:

1461492

Hom.:

698108

Cov.:

AF XY:

0.976

AC XY:

709428

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.969

Gnomad4 ASJ exome

AF:

0.971

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.980

Gnomad4 FIN exome

AF:

0.988

Gnomad4 NFE exome

AF:

0.989

Gnomad4 OTH exome

AF:

0.953

GnomAD4 genome

AF:

0.842

AC:

128105

AN:

152094

Hom.:

57809

Cov.:

AF XY:

0.846

AC XY:

62942

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.966

Gnomad4 EAS

AF:

0.989

Gnomad4 SAS

AF:

0.977

Gnomad4 FIN

AF:

0.988

Gnomad4 NFE

AF:

0.989

Gnomad4 OTH

AF:

0.881

Alfa

AF:

0.963

Hom.:

129414

Bravo

AF:

0.824

Asia WGS

AF:

0.948

AC:

3296

AN:

3478

EpiCase

AF:

0.988

EpiControl

AF:

0.987

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital diarrhea 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.6

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over