chr5-13841918-CAAAAAAAAAAA-C

Variant names:

• chr5-13841918-CAAAAAAAAAAA-C
• rs35337694
• NM_001369.3:c.5272-25_5272-15delTTTTTTTTTTT

Variant summary

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

The NM_001369.3(DNAH5):​c.5272-25_5272-15delTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 488,008 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 0 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

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5272-25_5272-15delTTTTTTTTTTT		intron_variant	Intron 32 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.5272-25_5272-15delTTTTTTTTTTT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5227-25_5227-15delTTTTTTTTTTT		intron_variant	Intron 32 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000205 AC: 1 AN: 488008 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 263784

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12568

American (AMR) AF: 0.00 AC: 0 AN: 19186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13880

East Asian (EAS) AF: 0.00 AC: 0 AN: 27146

South Asian (SAS) AF: 0.00 AC: 0 AN: 45024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1990

European-Non Finnish (NFE) AF: 0.00000316 AC: 1 AN: 316058

Other (OTH) AF: 0.00 AC: 0 AN: 25374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs35337694; hg19: chr5-13842027;