17-11598503-GGCTCGCGGAGGAGCGGGCCGC-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001372.4(DNAH9):c.14_34del(p.Glu5_Ala11del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,357,400 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: DNAH9 NM_001372.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001372.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH9	NM_001372.4	c.14_34del	p.Glu5_Ala11del	inframe_deletion	1/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9	c.14_34del	p.Glu5_Ala11del	inframe_deletion	1/69	1	NM_001372.4	P1
DNAH9	ENST00000579406.1	n.41_61del		non_coding_transcript_exon_variant	1/8	1
DNAH9	ENST00000454412.6	c.14_34del	p.Glu5_Ala11del	inframe_deletion	1/68	5
DNAH9	ENST00000579828.5	c.14_34del	p.Glu5_Ala11del	inframe_deletion	1/4	2

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150802 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000968

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 16 AN: 1206480 Hom.: 0 AF XY: 0.0000171 AC XY: 10 AN XY: 586434

Gnomad4 AFR exome AF: 0.0000420

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000254

Gnomad4 SAS exome AF: 0.0000380

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000403

Gnomad4 OTH exome AF: 0.0000402

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150920 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2 AN XY: 73762

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000968

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 23, 2022

This variant, c.14_34del, results in the deletion of 7 amino acid(s) of the DNAH9 protein (p.Glu5_Ala11del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNAH9-related conditions. ClinVar contains an entry for this variant (Variation ID: 1525609). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

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: rs1414498654; hg19: chr17-11501820;