chr17-11598539-A-ACGCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGAC

Variant names:

• chr17-11598539-A-ACGCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGAC
• NM_001372.4:c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001372.4(DNAH9):​c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG​(p.Arg24GlyfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 1,252,996 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: 31)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: DNAH9 NM_001372.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG	p.Arg24GlyfsTer28	frameshift_variant	Exon 1 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG	p.Arg24GlyfsTer28	frameshift_variant	Exon 1 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000579406.1	n.95_96insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG		non_coding_transcript_exon_variant	Exon 1 of 8	1
DNAH9	ENST00000454412.6	c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG	p.Arg24GlyfsTer28	frameshift_variant	Exon 1 of 68	5		ENSP00000414874.2
DNAH9	ENST00000579828.5	c.68_69insCGGATGGGGAACCCGGCGCCGACCGCGGATGGGGAACCCGGCGCCGACCG	p.Arg24GlyfsTer28	frameshift_variant	Exon 1 of 4	2		ENSP00000463782.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000239 AC: 3 AN: 1252996 Hom.: 0 Cov.: 33 AF XY: 0.00000490 AC XY: 3 AN XY: 611986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000294

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-11501856;