17-8121656-G-GGCA

Variant names:

• chr17-8121656-G-GGCA
• rs1406071405
• NM_001165967.2:c.605_607dupTGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001165967.2(HES7):​c.605_607dupTGC​(p.Leu202dup) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HES7 NM_001165967.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

Genes affected

HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES7	NM_001165967.2	c.605_607dupTGC	p.Leu202dup	conservative_inframe_insertion	Exon 4 of 4	ENST00000541682.7	NP_001159439.1
HES7	NM_032580.4	c.590_592dupTGC	p.Leu197dup	conservative_inframe_insertion	Exon 4 of 4		NP_115969.2
HES7	XM_047436940.1	c.701_703dupTGC	p.Leu234dup	conservative_inframe_insertion	Exon 3 of 3		XP_047292896.1
HES7	XM_047436941.1	c.692_694dupTGC	p.Leu231dup	conservative_inframe_insertion	Exon 5 of 5		XP_047292897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HES7	ENST00000541682.7	c.605_607dupTGC	p.Leu202dup	conservative_inframe_insertion	Exon 4 of 4	1	NM_001165967.2	ENSP00000446205.2
HES7	ENST00000317814.8	c.590_592dupTGC	p.Leu197dup	conservative_inframe_insertion	Exon 4 of 4	1		ENSP00000314774.4
HES7	ENST00000577735.1	c.*145_*147dupTGC		downstream_gene_variant		3		ENSP00000462491.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jun 14, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with HES7-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.590_592dup, results in the insertion of 1 amino acid(s) to the HES7 protein (p.Leu197dup), but otherwise preserves the integrity of the reading frame. -

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: rs1406071405; hg19: chr17-8024974;