chr5-13829499-G-A

Variant names:

• chr5-13829499-G-A
• rs1348691
• NM_001369.3:c.6444+11C>T

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.6444+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,558 control chromosomes in the GnomAD database, including 114,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12277 hom., cov: 32)
  • Exomes 𝑓: 0.37 (101975 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.07
• Publications: 5 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=-0.82).
• BP6: Variant 5-13829499-G-A is Benign according to our data. Variant chr5-13829499-G-A is described in ClinVar as Benign. ClinVar VariationId is 163144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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.6444+11C>T		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.6444+11C>T		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.6399+11C>T		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683090.1		n.1375+11C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60510 AN: 151878 Hom.: 12261 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.384 AC: 96539 AN: 251110 AF XY: 0.379

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.371 AC: 541690 AN: 1460562 Hom.: 101975 Cov.: 34 AF XY: 0.369 AC XY: 267884 AN XY: 726674

African (AFR) AF: 0.459 AC: 15356 AN: 33438

American (AMR) AF: 0.377 AC: 16877 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9388 AN: 26124

East Asian (EAS) AF: 0.562 AC: 22319 AN: 39688

South Asian (SAS) AF: 0.330 AC: 28440 AN: 86236

European-Finnish (FIN) AF: 0.328 AC: 17497 AN: 53418

Middle Eastern (MID) AF: 0.336 AC: 1914 AN: 5698

European-Non Finnish (NFE) AF: 0.366 AC: 406993 AN: 1110918

Other (OTH) AF: 0.380 AC: 22906 AN: 60334

GnomAD4 genome AF: 0.398 AC: 60563 AN: 151996 Hom.: 12277 Cov.: 32 AF XY: 0.396 AC XY: 29395 AN XY: 74288

African (AFR) AF: 0.461 AC: 19103 AN: 41420

American (AMR) AF: 0.383 AC: 5854 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1267 AN: 3464

East Asian (EAS) AF: 0.609 AC: 3148 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1596 AN: 4812

European-Finnish (FIN) AF: 0.318 AC: 3364 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24885 AN: 67984

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.384 Hom.: 2483

Bravo AF: 0.411

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 3 (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		1.1
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: rs1348691; hg19: chr5-13829608; COSMIC: COSV54258374;