5-13841918-CAAAAAAAAAA-CAAAAAAAAA

Position:

• chr5-13841918-CAAAAAAAAAA-CAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.5272-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (3668 hom., cov: 0)
  • Exomes 𝑓: 0.24 (381 hom.)
• Consequence: DNAH5 NM_001369.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 -16 ACMG points.

• BP6: Variant 5-13841918-CA-C is Benign according to our data. Variant chr5-13841918-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 351096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.5272-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.5272-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.5227-15del		splice_polypyrimidine_tract_variant, intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 32804 AN: 104540 Hom.: 3671 Cov.: 0

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.237 AC: 112952 AN: 475680 Hom.: 381 Cov.: 0 AF XY: 0.233 AC XY: 59978 AN XY: 256968

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.314 AC: 32792 AN: 104534 Hom.: 3668 Cov.: 0 AF XY: 0.317 AC XY: 14955 AN XY: 47224

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.334

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 05, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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;