18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_005257.6(GATA6):c.996_998dupCCA(p.His333dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00123 in 1,463,724 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. H333H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

GATA6
NM_005257.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.59

Publications

2 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

GATA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005257.6

BP6

Variant 18-22172111-T-TACC is Benign according to our data. Variant chr18-22172111-T-TACC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 404060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00151 (227/149996) while in subpopulation AFR AF = 0.00246 (101/41102). AF 95% confidence interval is 0.00207. There are 2 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.996_998dupCCA	p.His333dup	disruptive_inframe_insertion	Exon 2 of 7	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.996_998dupCCA	p.His333dup	disruptive_inframe_insertion	Exon 2 of 7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10 link	c.996_998dupCCA	p.His333dup	disruptive_inframe_insertion	Exon 2 of 7	1	NM_005257.6	ENSP00000269216.3		Q92908-1
GATA6	ENST00000581694.1 link	c.996_998dupCCA	p.His333dup	disruptive_inframe_insertion	Exon 1 of 6	1		ENSP00000462313.1		Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

229

AN:

149900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000924

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.000995

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.000196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00142

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00150

AC:

AN:

48518

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.000466

Gnomad FIN exome

AF:

0.00110

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.00119

AC:

1568

AN:

1313728

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

733

AN XY:

644874

show subpopulations

African (AFR)

AF:

0.00254

AC:

AN:

29154

American (AMR)

AF:

0.000742

AC:

AN:

32328

Ashkenazi Jewish (ASJ)

AF:

0.000787

AC:

AN:

21614

East Asian (EAS)

AF:

0.000619

AC:

AN:

32320

South Asian (SAS)

AF:

0.00118

AC:

AN:

72156

European-Finnish (FIN)

AF:

0.000886

AC:

AN:

29344

Middle Eastern (MID)

AF:

0.000396

AC:

AN:

5050

European-Non Finnish (NFE)

AF:

0.00122

AC:

1263

AN:

1037436

Other (OTH)

AF:

0.00105

AC:

AN:

54326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

138

206

275

344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

150

200

250

<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:

0.00151

AC:

227

AN:

149996

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

73208

show subpopulations

African (AFR)

AF:

0.00246

AC:

101

AN:

41102

American (AMR)

AF:

0.000857

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3444

East Asian (EAS)

AF:

0.000998

AC:

AN:

5012

South Asian (SAS)

AF:

0.00147

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.000196

AC:

AN:

10180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00142

AC:

AN:

67058

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000401

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 24, 2021

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 08, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

GATA6-related disorder

Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Atrioventricular septal defect 5

Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.6

Mutation Taster

=66/34

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over