5-13859634-G-T

Variant names:

• chr5-13859634-G-T
• rs1502043
• NM_001369.3:c.4797-29C>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.4797-29C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,608,722 control chromosomes in the GnomAD database, including 128,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10532 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118324 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.160
• Publications: 7 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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 5-13859634-G-T is Benign according to our data. Variant chr5-13859634-G-T is described in ClinVar as Benign. ClinVar VariationId is 258036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.4797-29C>A		intron	N/A	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.4797-29C>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.4752-29C>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55777 AN: 151930 Hom.: 10514 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.376 AC: 94187 AN: 250638 AF XY: 0.384

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.400 AC: 581944 AN: 1456674 Hom.: 118324 Cov.: 32 AF XY: 0.401 AC XY: 290682 AN XY: 724850

African (AFR) AF: 0.300 AC: 10015 AN: 33394

American (AMR) AF: 0.282 AC: 12615 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 8369 AN: 26096

East Asian (EAS) AF: 0.258 AC: 10221 AN: 39636

South Asian (SAS) AF: 0.450 AC: 38681 AN: 86042

European-Finnish (FIN) AF: 0.451 AC: 24091 AN: 53380

Middle Eastern (MID) AF: 0.325 AC: 1875 AN: 5762

European-Non Finnish (NFE) AF: 0.409 AC: 452988 AN: 1107438

Other (OTH) AF: 0.383 AC: 23089 AN: 60258

GnomAD4 genome AF: 0.367 AC: 55838 AN: 152048 Hom.: 10532 Cov.: 32 AF XY: 0.367 AC XY: 27238 AN XY: 74310

African (AFR) AF: 0.296 AC: 12277 AN: 41470

American (AMR) AF: 0.313 AC: 4788 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1091 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1339 AN: 5174

South Asian (SAS) AF: 0.447 AC: 2153 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4858 AN: 10560

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28162 AN: 67964

Other (OTH) AF: 0.372 AC: 785 AN: 2112

Alfa AF: 0.331 Hom.: 1548

Bravo AF: 0.348

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	0.38
DANN	Benign	0.51
PhyloP100		0.16
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: rs1502043; hg19: chr5-13859743; COSMIC: COSV54212389; COSMIC: COSV54212389;