12-14628744-GA-GAAAA

Position:

• chr12-14628744-GA-GAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004963.4(GUCY2C):​c.2158-10_2158-8dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: GUCY2C NM_004963.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY2C	NM_004963.4	c.2158-10_2158-8dupTTT		splice_region_variant, intron_variant		ENST00000261170.5	NP_004954.2
GUCY2C	XM_011520631.3	c.1912-10_1912-8dupTTT		splice_region_variant, intron_variant			XP_011518933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5	c.2158-10_2158-8dupTTT		splice_region_variant, intron_variant		1	NM_004963.4	ENSP00000261170.3

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150764 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000454 AC: 54 AN: 1188542 Hom.: 0 Cov.: 20 AF XY: 0.0000365 AC XY: 22 AN XY: 602912

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.0000495

Gnomad4 ASJ exome AF: 0.0000423

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.0000503

Gnomad4 OTH exome AF: 0.0000197

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150764 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73486

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3217210; hg19: chr12-14781678;