rs562588574

Variant names:

• chr18-22172111-TACCACCACCACCACC-T
• rs562588574
• NM_005257.6:c.984_998delCCACCACCACCACCA

Your query was ambiguous. Multiple possible variants found:

• chr18-22172111-TACCACCACCACCACC-T
• chr18-22172111-TACCACCACCACCACC-TACC
• chr18-22172111-TACCACCACCACCACC-TACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACCACCACC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005257.6(GATA6):​c.984_998delCCACCACCACCACCA​(p.His329_His333del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000457 in 1,313,808 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: GATA6 NM_005257.6 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59
• Publications: 2 publications found

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: Ambry Genetics, G2P
• atrioventricular septal defect 5

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics, Genomics England PanelApp
• 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
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005257.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005257.6. 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
	GATA6	NM_005257.6	MANE Select	c.984_998delCCACCACCACCACCA	p.His329_His333del	disruptive_inframe_deletion	Exon 2 of 7	NP_005248.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	ENST00000269216.10	TSL:1 MANE Select	c.984_998delCCACCACCACCACCA	p.His329_His333del	disruptive_inframe_deletion	Exon 2 of 7	ENSP00000269216.3	Q92908-1
	GATA6	ENST00000581694.1	TSL:1	c.984_998delCCACCACCACCACCA	p.His329_His333del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000462313.1	Q92908-1
	GATA6	ENST00000853536.1		c.984_998delCCACCACCACCACCA	p.His329_His333del	disruptive_inframe_deletion	Exon 2 of 8	ENSP00000523595.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000457 AC: 6 AN: 1313808 Hom.: 0 AF XY: 0.00000930 AC XY: 6 AN XY: 644914

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: 72162

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: 0.00000578 AC: 6 AN: 1037494

Other (OTH) AF: 0.00 AC: 0 AN: 54326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Atrioventricular septal defect 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

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

Other links and lift over

dbSNP: rs562588574; hg19: chr18-19752072;