8-23702248-T-C

Position:

• chr8-23702248-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136271.3(NKX2-6):​c.*203A>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 0.456 in 152,044 control chromosomes in the GnomAD database, including 16,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.46 (16041 hom., cov: 32)
• Consequence: NKX2-6 NM_001136271.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.644

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-23702248-T-C is Benign according to our data. Variant chr8-23702248-T-C is described in ClinVar as [Benign]. Clinvar id is 1271443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-6	NM_001136271.3	c.*203A>G		3_prime_UTR_variant	2/2	ENST00000325017.4
LOC107986930	XR_001745842.2	n.1312+33498T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-6	ENST00000325017.4	c.*203A>G		3_prime_UTR_variant	2/2	2	NM_001136271.3	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69348 AN: 151926 Hom.: 16031 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.456 AC: 69401 AN: 152044 Hom.: 16041 Cov.: 32 AF XY: 0.456 AC XY: 33916 AN XY: 74306

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.499

Alfa AF: 0.468 Hom.: 2106

Bravo AF: 0.454

Asia WGS AF: 0.453 AC: 1574 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7000862; hg19: chr8-23559761;