5-13845042-C-G

Variant names:

• chr5-13845042-C-G
• rs10041099
• NM_001369.3:c.5115-49G>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.5115-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,580,278 control chromosomes in the GnomAD database, including 105,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12616 hom., cov: 32)
  • Exomes 𝑓: 0.36 (92803 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.231
• Publications: 2 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=-0.86).
• BP6: Variant 5-13845042-C-G is Benign according to our data. Variant chr5-13845042-C-G is described in ClinVar as Benign. ClinVar VariationId is 258041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 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.5115-49G>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.5115-49G>C		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.5070-49G>C		intron	N/A	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60871 AN: 151728 Hom.: 12597 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.376 AC: 89974 AN: 239400 AF XY: 0.370

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.357 AC: 510369 AN: 1428432 Hom.: 92803 Cov.: 24 AF XY: 0.356 AC XY: 253454 AN XY: 712376

African (AFR) AF: 0.495 AC: 16100 AN: 32520

American (AMR) AF: 0.366 AC: 16054 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8742 AN: 25838

East Asian (EAS) AF: 0.559 AC: 21959 AN: 39302

South Asian (SAS) AF: 0.337 AC: 28596 AN: 84814

European-Finnish (FIN) AF: 0.326 AC: 17146 AN: 52546

Middle Eastern (MID) AF: 0.304 AC: 1733 AN: 5700

European-Non Finnish (NFE) AF: 0.349 AC: 378215 AN: 1084660

Other (OTH) AF: 0.368 AC: 21824 AN: 59232

GnomAD4 genome AF: 0.401 AC: 60932 AN: 151846 Hom.: 12616 Cov.: 32 AF XY: 0.398 AC XY: 29550 AN XY: 74210

African (AFR) AF: 0.499 AC: 20661 AN: 41380

American (AMR) AF: 0.371 AC: 5668 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3132 AN: 5152

South Asian (SAS) AF: 0.348 AC: 1668 AN: 4798

European-Finnish (FIN) AF: 0.316 AC: 3332 AN: 10532

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23962 AN: 67946

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.295 Hom.: 1139

Bravo AF: 0.413

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.30
PhyloP100		0.23
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: rs10041099; hg19: chr5-13845151; COSMIC: COSV54244753;