Genetic Variant NKX2-6:c.*46dupC (chr8-23702404-A-AG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001136271.3(NKX2-6):c.*46dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,420,068 control chromosomes in the GnomAD database, including 29,142 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2468 hom., cov: 30)

Exomes 𝑓: 0.20 ( 26674 hom. )

Consequence

NKX2-6
NM_001136271.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.192

Publications

0 publications found

Variant links:

COSMIC-nc: COSV107338474

Genes affected

NKX2-6 (HGNC:32940): (NK2 homeobox 6) This gene encodes a homeobox-containing protein that belongs to the NK-2 homeobox family. This protein is a vertebrate homolog of Drosophila homeobox-containing protein called 'tinman', which has been shown to be essential for development of the heart-like dorsal vessel. In conjunction with related gene, NKX2-5, this gene may play a role in both pharyngeal and cardiac embryonic development. Mutations in this gene are associated with persistent truncus arteriosus.[provided by RefSeq, Aug 2011]

NKX2-6 Gene-Disease associations (from GenCC):

conotruncal heart malformations
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital heart disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NKX2-6 links:

LOC107986930 (HGNC:):

LOC107986930 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-23702404-A-AG is Benign according to our data. Variant chr8-23702404-A-AG is described in ClinVar as Benign. ClinVar VariationId is 1276300.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136271.3. 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
	NKX2-6	NM_001136271.3	MANE Select	c.*46dupC		3_prime_UTR	Exon 2 of 2	NP_001129743.2	A6NCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-6	ENST00000325017.4	TSL:2 MANE Select	c.*46dupC		3_prime_UTR	Exon 2 of 2	ENSP00000320089.3	A6NCS4

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24707

AN:

152004

Hom.:

2467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.190

GnomAD2 exomes

AF:

0.194

AC:

11455

AN:

58932

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.0401

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.203

AC:

256853

AN:

1267946

Hom.:

26674

Cov.:

AF XY:

0.204

AC XY:

124787

AN XY:

612444

show subpopulations

African (AFR)

AF:

0.0359

AC:

991

AN:

27608

American (AMR)

AF:

0.213

AC:

4087

AN:

19146

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

4256

AN:

18518

East Asian (EAS)

AF:

0.232

AC:

7824

AN:

33744

South Asian (SAS)

AF:

0.226

AC:

13637

AN:

60410

European-Finnish (FIN)

AF:

0.236

AC:

7377

AN:

31200

Middle Eastern (MID)

AF:

0.210

AC:

923

AN:

4398

European-Non Finnish (NFE)

AF:

0.203

AC:

207381

AN:

1020174

Other (OTH)

AF:

0.197

AC:

10377

AN:

52748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

10402

20804

31207

41609

52011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7674

15348

23022

30696

38370

<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:

0.162

AC:

24708

AN:

152122

Hom.:

2468

Cov.:

AF XY:

0.166

AC XY:

12340

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0444

AC:

1847

AN:

41558

American (AMR)

AF:

0.209

AC:

3199

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

780

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1071

AN:

5142

South Asian (SAS)

AF:

0.220

AC:

1061

AN:

4812

European-Finnish (FIN)

AF:

0.235

AC:

2485

AN:

10578

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13724

AN:

67962

Other (OTH)

AF:

0.187

AC:

394

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1060

2120

3181

4241

5301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.182

Hom.:

339

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over