5-13886135-CAAAAAAAAAA-CAAAAAAAAA

Variant names:

• chr5-13886135-CA-C
• rs71600031
• NM_001369.3:c.2578-7delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.2578-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (817 hom., cov: 0)
  • Exomes 𝑓: 0.14 (142 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0110
• Publications: 2 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-13886135-CA-C is Benign according to our data. Variant chr5-13886135-CA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-7delT		splice_region_variant, intron_variant	Intron 17 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2578-7delT		splice_region_variant, intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-7delT		splice_region_variant, intron_variant	Intron 17 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10453delA		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.214-10453delA		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 15189 AN: 123680 Hom.: 818 Cov.: 0

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0591

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0827

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.102 AC: 6270 AN: 61536 AF XY: 0.0994

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.0795

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.145 AC: 170185 AN: 1175852 Hom.: 142 Cov.: 0 AF XY: 0.142 AC XY: 82622 AN XY: 580464

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

African (AFR) AF: 0.0974 AC: 2516 AN: 25824

American (AMR) AF: 0.0729 AC: 1920 AN: 26330

Ashkenazi Jewish (ASJ) AF: 0.0970 AC: 1954 AN: 20154

East Asian (EAS) AF: 0.175 AC: 5514 AN: 31584

South Asian (SAS) AF: 0.0881 AC: 5456 AN: 61902

European-Finnish (FIN) AF: 0.179 AC: 5329 AN: 29832

Middle Eastern (MID) AF: 0.112 AC: 388 AN: 3454

European-Non Finnish (NFE) AF: 0.151 AC: 140464 AN: 927646

Other (OTH) AF: 0.135 AC: 6644 AN: 49126

⚠️ 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 AF: 0.123 AC: 15190 AN: 123658 Hom.: 817 Cov.: 0 AF XY: 0.121 AC XY: 7092 AN XY: 58598

African (AFR) AF: 0.0795 AC: 2682 AN: 33756

American (AMR) AF: 0.0813 AC: 979 AN: 12038

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 210 AN: 3010

East Asian (EAS) AF: 0.121 AC: 433 AN: 3584

South Asian (SAS) AF: 0.0767 AC: 295 AN: 3844

European-Finnish (FIN) AF: 0.218 AC: 1301 AN: 5958

Middle Eastern (MID) AF: 0.0812 AC: 19 AN: 234

European-Non Finnish (NFE) AF: 0.154 AC: 9053 AN: 58764

Other (OTH) AF: 0.103 AC: 170 AN: 1658

Alfa AF: 0.0444 Hom.: 15

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:2

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 05, 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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs71600031; hg19: chr5-13886244; COSMIC: COSV54201919;