8-79766258-AGGCATGT-AGGCATGTGGCATGT

Variant names:

• chr8-79766258-A-AGGCATGT
• rs142613628
• NM_012258.4:c.331+386_331+392dupACATGCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001282851.2(HEY1):​c.-2_5dupACATGCC​(p.Leu3HisfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HEY1 NM_001282851.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 3 publications found

Genes affected

HEY1 (HGNC:4880): (hes related family bHLH transcription factor with YRPW motif 1) This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

LINC01607 (HGNC:51660): (long intergenic non-protein coding RNA 1607)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282851.2. 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
	HEY1	NM_012258.4	MANE Select	c.331+386_331+392dupACATGCC		intron	N/A	NP_036390.3
	HEY1	NM_001282851.2		c.-2_5dupACATGCC	p.Leu3HisfsTer4	frameshift	Exon 1 of 2	NP_001269780.1	B4DEI9
	HEY1	NM_001040708.2		c.343+386_343+392dupACATGCC		intron	N/A	NP_001035798.1	Q9Y5J3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEY1	ENST00000354724.8	TSL:1 MANE Select	c.331+386_331+392dupACATGCC		intron	N/A	ENSP00000346761.3	Q9Y5J3-1
	HEY1	ENST00000337919.9	TSL:1	c.343+386_343+392dupACATGCC		intron	N/A	ENSP00000338272.5	Q9Y5J3-2
	HEY1	ENST00000435063.4	TSL:1	n.142+102_142+108dupACATGCC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs142613628; hg19: chr8-80678493;