5-13841918-CAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr5-13841918-C-CA
• rs35337694
• NM_001369.3:c.5272-15dupT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001369.3(DNAH5):​c.5272-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (12437 hom., cov: 0)
  • Exomes 𝑓: 0.15 (97 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.617

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 5-13841918-C-CA is Benign according to our data. Variant chr5-13841918-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 351094.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5272-15dupT		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.5272-15_5272-14insT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5227-15_5227-14insT		intron_variant	Intron 32 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 50848 AN: 104496 Hom.: 12441 Cov.: 0

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.147 AC: 69437 AN: 473344 Hom.: 97 Cov.: 0 AF XY: 0.148 AC XY: 37774 AN XY: 255706

Gnomad4 AFR exome AF: 0.0990

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0886

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.486 AC: 50832 AN: 104490 Hom.: 12437 Cov.: 0 AF XY: 0.479 AC XY: 22584 AN XY: 47158

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.504

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 03, 2014	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35337694; hg19: chr5-13842027;