chr5-13841918-CAA-C

Variant names:

• chr5-13841918-CAA-C
• rs35337694
• NM_001369.3:c.5272-16_5272-15delTT

Variant summary

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

The NM_001369.3(DNAH5):​c.5272-16_5272-15delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 566,636 control chromosomes in the GnomAD database, including 427 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (411 hom., cov: 0)
  • Exomes 𝑓: 0.13 (16 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts 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 -16 ACMG points.

• BP6: Variant 5-13841918-CAA-C is Benign according to our data. Variant chr5-13841918-CAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 402728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5272-16_5272-15delTT		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.5272-16_5272-15delTT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5227-16_5227-15delTT		intron_variant	Intron 32 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 5686 AN: 104630 Hom.: 410 Cov.: 0

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.00337

Gnomad EAS AF: 0.00191

Gnomad SAS AF: 0.000741

Gnomad FIN AF: 0.00370

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0375

GnomAD4 exome AF: 0.133 AC: 61598 AN: 462012 Hom.: 16 AF XY: 0.131 AC XY: 32565 AN XY: 248950

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.0955

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.0544 AC: 5695 AN: 104624 Hom.: 411 Cov.: 0 AF XY: 0.0553 AC XY: 2614 AN XY: 47234

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.00337

Gnomad4 EAS AF: 0.00192

Gnomad4 SAS AF: 0.000742

Gnomad4 FIN AF: 0.00370

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.0374

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Primary ciliary dyskinesia Benign:1

Jul 30, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;