rs78594685

Variant names:

• chr5-13916319-T-C
• rs78594685
• NM_001369.3:c.1197+29A>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.1197+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,229,788 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (225 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (157 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0660
• Publications: 1 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=-0.89).
• BP6: Variant 5-13916319-T-C is Benign according to our data. Variant chr5-13916319-T-C is described in ClinVar as Benign. ClinVar VariationId is 257986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.1197+29A>G		intron_variant	Intron 9 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.1197+29A>G		intron_variant	Intron 9 of 78	1	NM_001369.3	ENSP00000265104.4

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4438 AN: 151878 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00963

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00820 AC: 2031 AN: 247650 AF XY: 0.00624

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00586

Gnomad ASJ exome AF: 0.00930

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000517

Gnomad OTH exome AF: 0.00366

GnomAD4 exome AF: 0.00366 AC: 3942 AN: 1077796 Hom.: 157 Cov.: 14 AF XY: 0.00318 AC XY: 1761 AN XY: 553092

African (AFR) AF: 0.107 AC: 2766 AN: 25866

American (AMR) AF: 0.00607 AC: 262 AN: 43158

Ashkenazi Jewish (ASJ) AF: 0.00859 AC: 198 AN: 23052

East Asian (EAS) AF: 0.0000819 AC: 3 AN: 36626

South Asian (SAS) AF: 0.000424 AC: 33 AN: 77742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51060

Middle Eastern (MID) AF: 0.00744 AC: 37 AN: 4972

European-Non Finnish (NFE) AF: 0.000342 AC: 263 AN: 768300

Other (OTH) AF: 0.00808 AC: 380 AN: 47020

GnomAD4 genome AF: 0.0293 AC: 4451 AN: 151992 Hom.: 225 Cov.: 32 AF XY: 0.0288 AC XY: 2140 AN XY: 74306

African (AFR) AF: 0.102 AC: 4222 AN: 41470

American (AMR) AF: 0.00962 AC: 147 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000295 AC: 20 AN: 67904

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0124 Hom.: 20

Bravo AF: 0.0329

Asia WGS AF: 0.00754 AC: 26 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.89
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.066
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: rs78594685; hg19: chr5-13916428;