rs2166337

Variant names:

• chr5-13692170-A-T
• rs2166337
• NM_001369.3:c.13724-35T>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.13724-35T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,611,270 control chromosomes in the GnomAD database, including 239,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (22763 hom., cov: 31)
  • Exomes 𝑓: 0.54 (216813 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.192
• Publications: 11 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 5-13692170-A-T is Benign according to our data. Variant chr5-13692170-A-T is described in ClinVar as Benign. ClinVar VariationId is 258001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 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.13724-35T>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.13724-35T>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.13679-35T>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683611.1		n.1057-35T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82803 AN: 151900 Hom.: 22737 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.551

GnomAD2 exomes AF: 0.523 AC: 128841 AN: 246408 AF XY: 0.518

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.544

Gnomad EAS exome AF: 0.429

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.532

GnomAD4 exome AF: 0.543 AC: 793072 AN: 1459252 Hom.: 216813 Cov.: 33 AF XY: 0.540 AC XY: 391790 AN XY: 725950

African (AFR) AF: 0.555 AC: 18527 AN: 33410

American (AMR) AF: 0.509 AC: 22693 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 14127 AN: 26094

East Asian (EAS) AF: 0.410 AC: 16223 AN: 39542

South Asian (SAS) AF: 0.437 AC: 37591 AN: 86118

European-Finnish (FIN) AF: 0.541 AC: 28848 AN: 53296

Middle Eastern (MID) AF: 0.516 AC: 2915 AN: 5652

European-Non Finnish (NFE) AF: 0.558 AC: 619859 AN: 1110228

Other (OTH) AF: 0.535 AC: 32289 AN: 60302

GnomAD4 genome AF: 0.545 AC: 82891 AN: 152018 Hom.: 22763 Cov.: 31 AF XY: 0.540 AC XY: 40112 AN XY: 74332

African (AFR) AF: 0.563 AC: 23339 AN: 41438

American (AMR) AF: 0.524 AC: 8005 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2319 AN: 5158

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5768 AN: 10582

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37561 AN: 67958

Other (OTH) AF: 0.554 AC: 1168 AN: 2108

Alfa AF: 0.541 Hom.: 4133

Bravo AF: 0.547

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		-0.19
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: rs2166337; hg19: chr5-13692279; COSMIC: COSV54261509;