5-13841918-CAAAAAAAAAA-CAAAAAAA

Position:

• chr5-13841918-CAAAAAAAAAA-CAAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001369.3(DNAH5):​c.5272-17_5272-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 572,562 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 0)
  • Exomes 𝑓: 0.038 (2 hom.)
• Consequence: DNAH5 NM_001369.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 5-13841918-CAAA-C is Benign according to our data. Variant chr5-13841918-CAAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3076106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.5272-17_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.5272-17_5272-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.5227-17_5227-15del		splice_polypyrimidine_tract_variant, intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 241 AN: 104630 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00807

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000690

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000319

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000530

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000730

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.0380 AC: 17774 AN: 467938 Hom.: 2 AF XY: 0.0368 AC XY: 9308 AN XY: 252780

Gnomad4 AFR exome AF: 0.0890

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.0368

Gnomad4 EAS exome AF: 0.0505

Gnomad4 SAS exome AF: 0.0251

Gnomad4 FIN exome AF: 0.0355

Gnomad4 NFE exome AF: 0.0363

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.00231 AC: 242 AN: 104624 Hom.: 1 Cov.: 0 AF XY: 0.00237 AC XY: 112 AN XY: 47244

Gnomad4 AFR AF: 0.00810

Gnomad4 AMR AF: 0.000690

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000320

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000530

Gnomad4 NFE AF: 0.0000730

Gnomad4 OTH AF: 0.00144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 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. -

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;