chr5-13814573-T-C

Variant names:

• chr5-13814573-T-C
• rs56046501
• NM_001369.3:c.7230+32A>G

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.7230+32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,607,442 control chromosomes in the GnomAD database, including 41,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4544 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36698 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.686
• Publications: 4 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=-0.66).
• BP6: Variant 5-13814573-T-C is Benign according to our data. Variant chr5-13814573-T-C is described in ClinVar as Benign. ClinVar VariationId is 258057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 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.7230+32A>G		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.7230+32A>G		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.7185+32A>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36189 AN: 152032 Hom.: 4542 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.229 AC: 57074 AN: 249230 AF XY: 0.224

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.217 AC: 315873 AN: 1455292 Hom.: 36698 Cov.: 31 AF XY: 0.215 AC XY: 155841 AN XY: 724368

African (AFR) AF: 0.280 AC: 9319 AN: 33288

American (AMR) AF: 0.200 AC: 8904 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4126 AN: 26084

East Asian (EAS) AF: 0.498 AC: 19742 AN: 39634

South Asian (SAS) AF: 0.168 AC: 14454 AN: 85984

European-Finnish (FIN) AF: 0.196 AC: 10417 AN: 53070

Middle Eastern (MID) AF: 0.144 AC: 831 AN: 5756

European-Non Finnish (NFE) AF: 0.212 AC: 234865 AN: 1106712

Other (OTH) AF: 0.220 AC: 13215 AN: 60170

GnomAD4 genome AF: 0.238 AC: 36218 AN: 152150 Hom.: 4544 Cov.: 32 AF XY: 0.235 AC XY: 17510 AN XY: 74384

African (AFR) AF: 0.278 AC: 11519 AN: 41498

American (AMR) AF: 0.208 AC: 3182 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2780 AN: 5164

South Asian (SAS) AF: 0.184 AC: 891 AN: 4830

European-Finnish (FIN) AF: 0.193 AC: 2038 AN: 10584

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14397 AN: 67992

Other (OTH) AF: 0.232 AC: 491 AN: 2112

Alfa AF: 0.221 Hom.: 728

Bravo AF: 0.246

Asia WGS AF: 0.316 AC: 1099 AN: 3478

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	-0.66
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.69
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: rs56046501; hg19: chr5-13814682;