rs17265718

Variant names:

• chr5-13817716-T-C
• rs17265718
• NM_001369.3:c.6842-22A>G

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.6842-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,612,932 control chromosomes in the GnomAD database, including 1,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (109 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1718 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16
• Publications: 3 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=-0.79).
• BP6: Variant 5-13817716-T-C is Benign according to our data. Variant chr5-13817716-T-C is described in ClinVar as Benign. ClinVar VariationId is 258055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.6842-22A>G		intron_variant	Intron 41 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.6842-22A>G		intron_variant	Intron 41 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.6797-22A>G		intron_variant	Intron 41 of 78			ENSP00000505288.1
DNAH5	ENST00000683090.1	n.1773-22A>G		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5100 AN: 152146 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.0403 AC: 10118 AN: 251196 AF XY: 0.0422

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0564

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0613

Gnomad NFE exome AF: 0.0495

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0446 AC: 65192 AN: 1460668 Hom.: 1718 Cov.: 30 AF XY: 0.0453 AC XY: 32938 AN XY: 726686

African (AFR) AF: 0.00651 AC: 218 AN: 33462

American (AMR) AF: 0.0178 AC: 796 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 1394 AN: 26120

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39686

South Asian (SAS) AF: 0.0530 AC: 4570 AN: 86194

European-Finnish (FIN) AF: 0.0618 AC: 3300 AN: 53394

Middle Eastern (MID) AF: 0.0480 AC: 277 AN: 5766

European-Non Finnish (NFE) AF: 0.0467 AC: 51875 AN: 1110970

Other (OTH) AF: 0.0457 AC: 2756 AN: 60360

GnomAD4 genome AF: 0.0335 AC: 5095 AN: 152264 Hom.: 109 Cov.: 33 AF XY: 0.0341 AC XY: 2535 AN XY: 74436

African (AFR) AF: 0.00861 AC: 358 AN: 41562

American (AMR) AF: 0.0259 AC: 396 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0450 AC: 217 AN: 4820

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3289 AN: 68022

Other (OTH) AF: 0.0265 AC: 56 AN: 2112

Alfa AF: 0.0420 Hom.: 325

Bravo AF: 0.0291

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Dec 18, 2019

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.64
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17265718; hg19: chr5-13817825;