Variant 12-14628744-GA-GAA 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.2158-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20634 hom., cov: 0)

Exomes 𝑓: 0.41 ( 83127 hom. )

Consequence

GUCY2C
NM_004963.4 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.995

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-14628744-G-GA is Benign according to our data. Variant chr12-14628744-G-GA is described in ClinVar as [Benign]. Clinvar id is 402915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 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.2158-8dupT		splice_region_variant, intron_variant		ENST00000261170.5	NP_004954.2	P25092
GUCY2C	XM_011520631.3 linkuse as main transcript	c.1912-8dupT		splice_region_variant, intron_variant			XP_011518933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5 linkuse as main transcript	c.2158-8dupT		splice_region_variant, intron_variant		1	NM_004963.4	ENSP00000261170.3		P25092

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

77720

AN:

150654

Hom.:

20588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.447

AC:

96986

AN:

216742

Hom.:

18817

AF XY:

0.439

AC XY:

51764

AN XY:

117828

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.432

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.437

GnomAD4 exome

AF:

0.408

AC:

481838

AN:

1181968

Hom.:

83127

Cov.:

AF XY:

0.409

AC XY:

245394

AN XY:

599572

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.447

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.394

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.516

AC:

77834

AN:

150768

Hom.:

20634

Cov.:

AF XY:

0.517

AC XY:

37996

AN XY:

73550

show subpopulations

Gnomad4 AFR

AF:

0.609

Gnomad4 AMR

AF:

0.635

Gnomad4 ASJ

AF:

0.496

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.453

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.504

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	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

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