NM_001369.3:c.2578-9_2578-7dupTTT

Variant names:

• chr5-13886135-C-CAAA
• rs71600031
• NM_001369.3:c.2578-9_2578-7dupTTT

Variant summary

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

The NM_001369.3(DNAH5):​c.2578-9_2578-7dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5-AS1 (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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.2578-9_2578-7dupTTT		splice_region intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-10437_118-10435dupAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2578-7_2578-6insTTT		splice_region intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.2533-7_2533-6insTTT		splice_region intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-10454_254-10453insAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 123882 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 162 AN: 1218030 Hom.: 0 Cov.: 0 AF XY: 0.000133 AC XY: 80 AN XY: 602276

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

African (AFR) AF: 0.000448 AC: 12 AN: 26782

American (AMR) AF: 0.000292 AC: 8 AN: 27412

Ashkenazi Jewish (ASJ) AF: 0.000287 AC: 6 AN: 20872

East Asian (EAS) AF: 0.000303 AC: 10 AN: 32950

South Asian (SAS) AF: 0.000489 AC: 32 AN: 65490

European-Finnish (FIN) AF: 0.0000638 AC: 2 AN: 31358

Middle Eastern (MID) AF: 0.000282 AC: 1 AN: 3548

European-Non Finnish (NFE) AF: 0.0000928 AC: 89 AN: 958726

Other (OTH) AF: 0.0000393 AC: 2 AN: 50892

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 123882 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 58714

African (AFR) AF: 0.00 AC: 0 AN: 33766

American (AMR) AF: 0.00 AC: 0 AN: 12046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3012

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 3878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58874

Other (OTH) AF: 0.00 AC: 0 AN: 1656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.011

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71600031;

hg19: chr5-13886244;