NM_001369.3:c.2578-16_2578-7delTTTTTTTTTT

Variant names:

• chr5-13886135-CAAAAAAAAAA-C
• rs71600031
• NM_001369.3:c.2578-16_2578-7delTTTTTTTTTT

Variant summary

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

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
• Publications: 2 publications found

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]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.2578-16_2578-7delTTTTTTTTTT		splice_region intron	N/A	NP_001360.1
	DNAH5-AS1	NR_199035.1		n.118-10444_118-10435delAAAAAAAAAA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2578-16_2578-7delTTTTTTTTTT		splice_region intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.2533-16_2533-7delTTTTTTTTTT		splice_region intron	N/A	ENSP00000505288.1
	ENSG00000251423	ENST00000503244.2	TSL:4	n.254-10453_254-10444delAAAAAAAAAA		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 26790

American (AMR) AF: 0.000255 AC: 7 AN: 27426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20886

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 32998

South Asian (SAS) AF: 0.00 AC: 0 AN: 65544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3550

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 959020

Other (OTH) AF: 0.00 AC: 0 AN: 50910

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs71600031; hg19: chr5-13886244;