NM_001369.3:c.975+30A>C

Variant names:

• chr5-13919146-T-G
• rs35925547
• NM_001369.3:c.975+30A>C

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.975+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,530 control chromosomes in the GnomAD database, including 62,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4585 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57700 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.172
• Publications: 6 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=-0.83).
• BP6: Variant 5-13919146-T-G is Benign according to our data. Variant chr5-13919146-T-G is described in ClinVar as Benign. ClinVar VariationId is 258072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.975+30A>C		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.975+30A>C		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000682376.1		n.1049A>C		non_coding_transcript_exon	Exon 7 of 8
	DNAH5	ENST00000682586.1		n.1098A>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34635 AN: 152070 Hom.: 4577 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.261 AC: 65253 AN: 250400 AF XY: 0.269

Gnomad AFR exome AF: 0.0911

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.0827

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.276 AC: 403602 AN: 1461344 Hom.: 57700 Cov.: 34 AF XY: 0.279 AC XY: 202626 AN XY: 727016

African (AFR) AF: 0.0839 AC: 2808 AN: 33464

American (AMR) AF: 0.246 AC: 11013 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 8122 AN: 26128

East Asian (EAS) AF: 0.0953 AC: 3783 AN: 39690

South Asian (SAS) AF: 0.348 AC: 30024 AN: 86240

European-Finnish (FIN) AF: 0.301 AC: 16087 AN: 53394

Middle Eastern (MID) AF: 0.218 AC: 1254 AN: 5754

European-Non Finnish (NFE) AF: 0.283 AC: 314694 AN: 1111606

Other (OTH) AF: 0.262 AC: 15817 AN: 60356

GnomAD4 genome AF: 0.228 AC: 34670 AN: 152186 Hom.: 4585 Cov.: 32 AF XY: 0.231 AC XY: 17182 AN XY: 74388

African (AFR) AF: 0.0921 AC: 3828 AN: 41554

American (AMR) AF: 0.257 AC: 3919 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3472

East Asian (EAS) AF: 0.0893 AC: 462 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1662 AN: 4822

European-Finnish (FIN) AF: 0.323 AC: 3414 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19375 AN: 67998

Other (OTH) AF: 0.250 AC: 527 AN: 2110

Alfa AF: 0.266 Hom.: 1969

Bravo AF: 0.214

Asia WGS AF: 0.228 AC: 795 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.17
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: rs35925547; hg19: chr5-13919255; COSMIC: COSV54261195;