NM_001369.3:c.1198-24C>A

Variant names:

• chr5-13914666-G-T
• rs13180591
• NM_001369.3:c.1198-24C>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.1198-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,603,154 control chromosomes in the GnomAD database, including 131,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15255 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116627 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.139
• Publications: 9 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 5-13914666-G-T is Benign according to our data. Variant chr5-13914666-G-T is described in ClinVar as Benign. ClinVar VariationId is 257987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 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.1198-24C>A		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.1198-24C>A		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000682376.1		n.4842C>A		non_coding_transcript_exon	Exon 8 of 8
	DNAH5	ENST00000683967.1		n.2978C>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66240 AN: 151712 Hom.: 15251 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.421 AC: 105197 AN: 250068 AF XY: 0.414

Gnomad AFR exome AF: 0.535

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.861

Gnomad FIN exome AF: 0.331

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.390 AC: 566314 AN: 1451324 Hom.: 116627 Cov.: 33 AF XY: 0.388 AC XY: 280566 AN XY: 722300

African (AFR) AF: 0.534 AC: 17708 AN: 33174

American (AMR) AF: 0.395 AC: 17648 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 10969 AN: 26022

East Asian (EAS) AF: 0.841 AC: 33292 AN: 39590

South Asian (SAS) AF: 0.357 AC: 30721 AN: 86020

European-Finnish (FIN) AF: 0.339 AC: 18012 AN: 53170

Middle Eastern (MID) AF: 0.429 AC: 2385 AN: 5554

European-Non Finnish (NFE) AF: 0.373 AC: 410961 AN: 1103080

Other (OTH) AF: 0.410 AC: 24618 AN: 60054

GnomAD4 genome AF: 0.436 AC: 66271 AN: 151830 Hom.: 15255 Cov.: 32 AF XY: 0.435 AC XY: 32270 AN XY: 74216

African (AFR) AF: 0.528 AC: 21873 AN: 41442

American (AMR) AF: 0.412 AC: 6285 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1419 AN: 3464

East Asian (EAS) AF: 0.853 AC: 4401 AN: 5162

South Asian (SAS) AF: 0.372 AC: 1790 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3454 AN: 10556

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25726 AN: 67818

Other (OTH) AF: 0.428 AC: 904 AN: 2114

Alfa AF: 0.403 Hom.: 38205

Bravo AF: 0.450

Asia WGS AF: 0.572 AC: 1988 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 10, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		0.14
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: rs13180591; hg19: chr5-13914775;