chr18-22177952-G-T

Variant names:

• chr18-22177952-G-T
• rs7235350
• NM_005257.6:c.1302+831G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005257.6(GATA6):​c.1302+831G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2424 hom., cov: 16)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 1 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: 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: Ambry Genetics, G2P, Genomics England PanelApp, Orphanet, 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
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	NM_005257.6	MANE Select	c.1302+831G>T		intron	N/A	NP_005248.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	ENST00000269216.10	TSL:1 MANE Select	c.1302+831G>T		intron	N/A	ENSP00000269216.3	Q92908-1
	GATA6	ENST00000581694.1	TSL:1	c.1302+831G>T		intron	N/A	ENSP00000462313.1	Q92908-1
	GATA6	ENST00000853536.1		c.1303-218G>T		intron	N/A	ENSP00000523595.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 14664 AN: 77886 Hom.: 2409 Cov.: 16

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 14705 AN: 77924 Hom.: 2424 Cov.: 16 AF XY: 0.194 AC XY: 7211 AN XY: 37148

African (AFR) AF: 0.516 AC: 10433 AN: 20236

American (AMR) AF: 0.187 AC: 1431 AN: 7670

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 140 AN: 2010

East Asian (EAS) AF: 0.105 AC: 290 AN: 2762

South Asian (SAS) AF: 0.130 AC: 287 AN: 2208

European-Finnish (FIN) AF: 0.0485 AC: 187 AN: 3858

Middle Eastern (MID) AF: 0.123 AC: 14 AN: 114

European-Non Finnish (NFE) AF: 0.0463 AC: 1734 AN: 37486

Other (OTH) AF: 0.170 AC: 179 AN: 1050

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7235350;

hg19: chr18-19757913;