chr5-13841918-CAAAAAAAA-C

Variant names:

• chr5-13841918-CAAAAAAAA-C
• rs35337694
• NM_001369.3:c.5272-22_5272-15delTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369.3(DNAH5):​c.5272-22_5272-15delTTTTTTTT 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 487,996 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: 0)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5272-22_5272-15delTTTTTTTT		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.5272-22_5272-15delTTTTTTTT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5227-22_5227-15delTTTTTTTT		intron_variant	Intron 32 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000205 AC: 1 AN: 487996 Hom.: 0 AF XY: 0.00000379 AC XY: 1 AN XY: 263778

⚠️ 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: 19182

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 27142

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: 316054

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		0.96

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;