Variant 12-14681487-GAA-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004963.4(GUCY2C):c.612-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67306 hom., cov: 0)

Exomes 𝑓: 0.99 ( 717027 hom. )

Consequence

GUCY2C
NM_004963.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.225

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:

GUCY2C-AS1 (HGNC:56054): (GUCY2C antisense RNA 1)

GUCY2C-AS1 links:

C12orf60 (HGNC:):

C12orf60 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-14681487-GA-G is Benign according to our data. Variant chr12-14681487-GA-G is described in ClinVar as [Benign]. Clinvar id is 402917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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.612-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261170.5	NP_004954.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
GUCY2C	ENST00000261170.5 linkuse as main transcript	c.612-11del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_004963.4	ENSP00000261170	P1
GUCY2C-AS1	ENST00000501178.2 linkuse as main transcript	n.247+9178del	intron_variant, non_coding_transcript_variant	3
GUCY2C	ENST00000535803.1 linkuse as main transcript	n.739-11del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142111

AN:

151814

Hom.:

67271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.996

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.954

GnomAD3 exomes

AF:

0.981

AC:

245163

AN:

249906

Hom.:

120655

AF XY:

0.986

AC XY:

133153

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.989

Gnomad ASJ exome

AF:

0.990

Gnomad EAS exome

AF:

0.985

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.990

GnomAD4 exome

AF:

0.992

AC:

1443284

AN:

1454380

Hom.:

717027

Cov.:

AF XY:

0.993

AC XY:

719115

AN XY:

724016

show subpopulations

Gnomad4 AFR exome

AF:

0.772

Gnomad4 AMR exome

AF:

0.987

Gnomad4 ASJ exome

AF:

0.991

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.983

GnomAD4 genome

AF:

0.936

AC:

142202

AN:

151932

Hom.:

67306

Cov.:

AF XY:

0.937

AC XY:

69602

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.782

Gnomad4 AMR

AF:

0.975

Gnomad4 ASJ

AF:

0.989

Gnomad4 EAS

AF:

0.985

Gnomad4 SAS

AF:

0.998

Gnomad4 FIN

AF:

0.996

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.954

Alfa

AF:

0.971

Hom.:

13063

Bravo

AF:

0.928

Asia WGS

AF:

0.977

AC:

3399

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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