rs7704417

Variant names:

• chr5-13862507-C-T
• rs7704417
• NM_001369.3:c.4796+41G>A

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.4796+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,573,626 control chromosomes in the GnomAD database, including 129,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11963 hom., cov: 31)
  • Exomes 𝑓: 0.40 (117661 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.79
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-13862507-C-T is Benign according to our data. Variant chr5-13862507-C-T is described in ClinVar as [Benign]. Clinvar id is 258035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.4796+41G>A		intron_variant	Intron 29 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.4796+41G>A		intron_variant	Intron 29 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.4751+41G>A		intron_variant	Intron 29 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.253+1952C>T		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.213+1992C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59820 AN: 151720 Hom.: 11947 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.385 AC: 96122 AN: 249376 AF XY: 0.392

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.325

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.404 AC: 573751 AN: 1421790 Hom.: 117661 Cov.: 24 AF XY: 0.405 AC XY: 287719 AN XY: 709762

African (AFR) AF: 0.392 AC: 12830 AN: 32694

American (AMR) AF: 0.290 AC: 12897 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8392 AN: 25846

East Asian (EAS) AF: 0.258 AC: 10177 AN: 39416

South Asian (SAS) AF: 0.472 AC: 40275 AN: 85318

European-Finnish (FIN) AF: 0.454 AC: 24161 AN: 53240

Middle Eastern (MID) AF: 0.333 AC: 1899 AN: 5708

European-Non Finnish (NFE) AF: 0.409 AC: 440029 AN: 1076066

Other (OTH) AF: 0.391 AC: 23091 AN: 58986

GnomAD4 genome AF: 0.394 AC: 59888 AN: 151836 Hom.: 11963 Cov.: 31 AF XY: 0.393 AC XY: 29167 AN XY: 74232

African (AFR) AF: 0.386 AC: 15959 AN: 41360

American (AMR) AF: 0.330 AC: 5035 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1348 AN: 5166

South Asian (SAS) AF: 0.467 AC: 2243 AN: 4802

European-Finnish (FIN) AF: 0.463 AC: 4880 AN: 10542

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28106 AN: 67932

Other (OTH) AF: 0.394 AC: 829 AN: 2106

Alfa AF: 0.396 Hom.: 30895

Bravo AF: 0.379

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.95
CADD	Benign	0.020
DANN	Benign	0.60
PhyloP100		-2.8
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: rs7704417; hg19: chr5-13862616; COSMIC: COSV54212407;