rs780012501

Variant names:

• chr8-23703008-CGCCGCTGTT-C
• rs780012501
• NM_001136271.3:c.340_348delAACAGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr8-23703008-CGCCGCTGTT-C
• chr8-23703008-CGCCGCTGTT-CGCCGCTGTTGCCGCTGTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001136271.3(NKX2-6):​c.340_348delAACAGCGGC​(p.Asn114_Gly116del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,700 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NKX2-6 NM_001136271.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LOC107986930 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001136271.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-6	NM_001136271.3	c.340_348delAACAGCGGC	p.Asn114_Gly116del	conservative_inframe_deletion	Exon 2 of 2	ENST00000325017.4	NP_001129743.2
LOC107986930	XR_001745842.2	n.1312+34262_1312+34270delGCTGTTGCC		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-6	ENST00000325017.4	c.340_348delAACAGCGGC	p.Asn114_Gly116del	conservative_inframe_deletion	Exon 2 of 2	2	NM_001136271.3	ENSP00000320089.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388700 Hom.: 0 AF XY: 0.00000146 AC XY: 1 AN XY: 685022

African (AFR) AF: 0.00 AC: 0 AN: 31426

American (AMR) AF: 0.00 AC: 0 AN: 35548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25070

East Asian (EAS) AF: 0.00 AC: 0 AN: 35640

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 79022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4884

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077492

Other (OTH) AF: 0.00 AC: 0 AN: 57720

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs780012501; hg19: chr8-23560521;