GeneBe

18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACCACCACC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_005257.6(GATA6):​c.990_998dupCCACCACCA​(p.His331_His333dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000152 in 1,313,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H333H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GATA6
NM_005257.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59

Publications

0 publications found
Variant links:
Genes affected
GATA6 (HGNC:4174): (GATA binding protein 6) This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012]
GATA6 Gene-Disease associations (from GenCC):
  • atrial septal defect 9
    Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics
  • atrioventricular septal defect 5
    Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • pancreatic hypoplasia-diabetes-congenital heart disease syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • metabolic syndrome
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • neonatal diabetes mellitus
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • tetralogy of fallot
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • familial atrial fibrillation
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • conotruncal heart malformations
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_005257.6

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA6NM_005257.6 linkc.990_998dupCCACCACCA p.His331_His333dup disruptive_inframe_insertion Exon 2 of 7 ENST00000269216.10 NP_005248.2 Q92908-1
GATA6XM_047437483.1 linkc.990_998dupCCACCACCA p.His331_His333dup disruptive_inframe_insertion Exon 2 of 7 XP_047293439.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA6ENST00000269216.10 linkc.990_998dupCCACCACCA p.His331_His333dup disruptive_inframe_insertion Exon 2 of 7 1 NM_005257.6 ENSP00000269216.3 Q92908-1
GATA6ENST00000581694.1 linkc.990_998dupCCACCACCA p.His331_His333dup disruptive_inframe_insertion Exon 1 of 6 1 ENSP00000462313.1 Q92908-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000152
AC:
2
AN:
1313812
Hom.:
0
Cov.:
31
AF XY:
0.00000155
AC XY:
1
AN XY:
644916
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
29160
American (AMR)
AF:
0.00
AC:
0
AN:
32330
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21614
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32324
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72164
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
29348
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5050
European-Non Finnish (NFE)
AF:
0.00000193
AC:
2
AN:
1037496
Other (OTH)
AF:
0.00
AC:
0
AN:
54326
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.6

Splicing

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

Publications

Other links and lift over

dbSNP: rs562588574; hg19: chr18-19752072; API