chr5-13886135-CAAAAAAAAAA-C

Position:

• chr5-13886135-CAAAAAAAAAA-C

Variant summary

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

The NM_001369.3(DNAH5):​c.2578-16_2578-7delTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000739 in 1,218,492 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: 0)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

ENSG00000251423 (HGNC:):

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/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-16_2578-7delTTTTTTTTTT		splice_region_variant, intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2578-16_2578-7delTTTTTTTTTT		splice_region_variant, intron_variant		1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-16_2533-7delTTTTTTTTTT		splice_region_variant, intron_variant				ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10444_254-10435delAAAAAAAAAA		intron_variant		4
ENSG00000251423	ENST00000637153.1	n.214-10444_214-10435delAAAAAAAAAA		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000739 AC: 9 AN: 1218492 Hom.: 0 AF XY: 0.00000664 AC XY: 4 AN XY: 602484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000303

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

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

LitVar

Other links and lift over

dbSNP: rs71600031; hg19: chr5-13886244;