chr18-22200900-A-G

Variant names:

• chr18-22200900-A-G
• rs1941083
• NM_005257.6:c.*77A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005257.6(GATA6):​c.*77A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,449,538 control chromosomes in the GnomAD database, including 14,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1470 hom., cov: 33)
  • Exomes 𝑓: 0.14 (13476 hom.)
• Consequence: GATA6 NM_005257.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.116
• Publications: 7 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: 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

ENSG00000266283 (HGNC:58686):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-22200900-A-G is Benign according to our data. Variant chr18-22200900-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	NM_005257.6	MANE Select	c.*77A>G		3_prime_UTR	Exon 7 of 7	NP_005248.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	ENST00000269216.10	TSL:1 MANE Select	c.*77A>G		3_prime_UTR	Exon 7 of 7	ENSP00000269216.3
	GATA6	ENST00000853536.1		c.*77A>G		3_prime_UTR	Exon 8 of 8	ENSP00000523595.1
	GATA6	ENST00000853535.1		c.*77A>G		3_prime_UTR	Exon 7 of 7	ENSP00000523594.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18651 AN: 152152 Hom.: 1464 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.142 AC: 183992 AN: 1297268 Hom.: 13476 Cov.: 20 AF XY: 0.143 AC XY: 91494 AN XY: 641252

African (AFR) AF: 0.0246 AC: 730 AN: 29730

American (AMR) AF: 0.221 AC: 7825 AN: 35356

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2449 AN: 24064

East Asian (EAS) AF: 0.153 AC: 5460 AN: 35696

South Asian (SAS) AF: 0.152 AC: 11929 AN: 78652

European-Finnish (FIN) AF: 0.146 AC: 5934 AN: 40634

Middle Eastern (MID) AF: 0.162 AC: 623 AN: 3854

European-Non Finnish (NFE) AF: 0.142 AC: 141560 AN: 995020

Other (OTH) AF: 0.138 AC: 7482 AN: 54262

GnomAD4 genome AF: 0.123 AC: 18667 AN: 152270 Hom.: 1470 Cov.: 33 AF XY: 0.128 AC XY: 9546 AN XY: 74450

African (AFR) AF: 0.0316 AC: 1314 AN: 41582

American (AMR) AF: 0.221 AC: 3385 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3468

East Asian (EAS) AF: 0.185 AC: 955 AN: 5170

South Asian (SAS) AF: 0.142 AC: 687 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10604

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9830 AN: 68004

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.133 Hom.: 187

Bravo AF: 0.121

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1941083; hg19: chr18-19780863; COSMIC: COSV52525660; COSMIC: COSV52525660;