rs3217210

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_004963.4(GUCY2C):c.2158-8delT 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 0.00080 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00088 ( 4 hom. )

Consequence

GUCY2C
NM_004963.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.995

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

congenital diarrhea 6
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
congenital sodium diarrhea
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GUCY2C links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004963.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-14628744-GA-G is Benign according to our data. Variant chr12-14628744-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1668452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000802 (121/150880) while in subpopulation EAS AF = 0.000974 (5/5132). AF 95% confidence interval is 0.000615. There are 0 homozygotes in GnomAd4. There are 53 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004963.4. 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
	GUCY2C	NM_004963.4	MANE Select	c.2158-8delT		splice_region intron	N/A	NP_004954.2	P25092

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GUCY2C	ENST00000261170.5	TSL:1 MANE Select	c.2158-8delT	splice_region intron	N/A	ENSP00000261170.3	P25092
GUCY2C	ENST00000867619.1		c.2191-8delT	splice_region intron	N/A	ENSP00000537678.1
GUCY2C	ENST00000970783.1		c.2158-8delT	splice_region intron	N/A	ENSP00000640842.1

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

121

AN:

150766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000585

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.000331

Gnomad ASJ

AF:

0.00781

Gnomad EAS

AF:

0.000972

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.0000975

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000783

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000867

AC:

188

AN:

216742

AF XY:

0.000874

show subpopulations

Gnomad AFR exome

AF:

0.000721

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00731

Gnomad EAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.000154

Gnomad NFE exome

AF:

0.000684

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000880

AC:

1046

AN:

1188842

Hom.:

Cov.:

AF XY:

0.000899

AC XY:

542

AN XY:

603030

show subpopulations

African (AFR)

AF:

0.000646

AC:

AN:

26318

American (AMR)

AF:

0.000173

AC:

AN:

40390

Ashkenazi Jewish (ASJ)

AF:

0.00672

AC:

159

AN:

23672

East Asian (EAS)

AF:

0.00100

AC:

AN:

37844

South Asian (SAS)

AF:

0.000463

AC:

AN:

77788

European-Finnish (FIN)

AF:

0.000214

AC:

AN:

51446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5142

European-Non Finnish (NFE)

AF:

0.000825

AC:

722

AN:

875520

Other (OTH)

AF:

0.00110

AC:

AN:

50722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000802

AC:

121

AN:

150880

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

AN XY:

73614

show subpopulations

African (AFR)

AF:

0.000583

AC:

AN:

41146

American (AMR)

AF:

0.000330

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

AN:

3458

East Asian (EAS)

AF:

0.000974

AC:

AN:

5132

South Asian (SAS)

AF:

0.000837

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.0000975

AC:

AN:

10260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000783

AC:

AN:

67692

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000552

Hom.:

8258

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over