8-23702404-A-AG

Position:

• chr8-23702404-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001136271.3(NKX2-6):​c.*46_*47insC 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.192

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]

LOC107986930 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-6	NM_001136271.3	c.*46_*47insC		3_prime_UTR_variant	2/2	ENST00000325017.4
LOC107986930	XR_001745842.2	n.1312+33657dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-6	ENST00000325017.4	c.*46_*47insC		3_prime_UTR_variant	2/2	2	NM_001136271.3	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24707 AN: 152004 Hom.: 2467 Cov.: 30

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

GnomAD3 exomes AF: 0.194 AC: 11455 AN: 58932 Hom.: 1156 AF XY: 0.196 AC XY: 5811 AN XY: 29700

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 SAS exome AF: 0.219

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.: 31 AF XY: 0.204 AC XY: 124787 AN XY: 612444

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.162 AC: 24708 AN: 152122 Hom.: 2468 Cov.: 30 AF XY: 0.166 AC XY: 12340 AN XY: 74342

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.187

Alfa AF: 0.182 Hom.: 339

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146685693; hg19: chr8-23559917;