NM_001369.3:c.7609+19C>T

Variant names:

• chr5-13810040-G-A
• rs35732567
• NM_001369.3:c.7609+19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.7609+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,549,262 control chromosomes in the GnomAD database, including 117,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11042 hom., cov: 32)
  • Exomes 𝑓: 0.39 (106521 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0950
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-13810040-G-A is Benign according to our data. Variant chr5-13810040-G-A is described in ClinVar as Benign. ClinVar VariationId is 197516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.7609+19C>T		intron_variant	Intron 45 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.7609+19C>T		intron_variant	Intron 45 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.7564+19C>T		intron_variant	Intron 45 of 78			ENSP00000505288.1
DNAH5	ENST00000512443.1	n.465+19C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57223 AN: 151922 Hom.: 11038 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.393

GnomAD2 exomes AF: 0.393 AC: 60520 AN: 154048 AF XY: 0.390

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.646

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.388 AC: 542739 AN: 1397226 Hom.: 106521 Cov.: 35 AF XY: 0.387 AC XY: 266642 AN XY: 689292

African (AFR) AF: 0.327 AC: 10313 AN: 31578

American (AMR) AF: 0.406 AC: 14558 AN: 35844

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9041 AN: 25154

East Asian (EAS) AF: 0.573 AC: 20544 AN: 35856

South Asian (SAS) AF: 0.342 AC: 27066 AN: 79204

European-Finnish (FIN) AF: 0.362 AC: 17781 AN: 49160

Middle Eastern (MID) AF: 0.364 AC: 1481 AN: 4068

European-Non Finnish (NFE) AF: 0.389 AC: 419427 AN: 1078568

Other (OTH) AF: 0.390 AC: 22528 AN: 57794

GnomAD4 genome AF: 0.377 AC: 57252 AN: 152036 Hom.: 11042 Cov.: 32 AF XY: 0.376 AC XY: 27921 AN XY: 74302

African (AFR) AF: 0.325 AC: 13490 AN: 41478

American (AMR) AF: 0.399 AC: 6101 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3224 AN: 5162

South Asian (SAS) AF: 0.345 AC: 1659 AN: 4812

European-Finnish (FIN) AF: 0.353 AC: 3729 AN: 10576

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26371 AN: 67940

Other (OTH) AF: 0.389 AC: 820 AN: 2106

Alfa AF: 0.378 Hom.: 3763

Bravo AF: 0.381

Asia WGS AF: 0.450 AC: 1562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 16, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 3 Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs35732567; hg19: chr5-13810149;