rs13170062

Variant names:

• chr5-13882849-C-T
• rs13170062
• NM_001369.3:c.3175-34G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-13882849-C-T
• chr5-13882849-C-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.3175-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,216 control chromosomes in the GnomAD database, including 73,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6152 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67801 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.197
• 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

DNAH5-AS1 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-13882849-C-T is Benign according to our data. Variant chr5-13882849-C-T is described in ClinVar as Benign. ClinVar VariationId is 258017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 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.3175-34G>A		intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-13740C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.3175-34G>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.3130-34G>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-13740C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41876 AN: 151870 Hom.: 6152 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.314 AC: 78936 AN: 251262 AF XY: 0.313

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.597

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.299 AC: 437224 AN: 1461228 Hom.: 67801 Cov.: 34 AF XY: 0.299 AC XY: 217313 AN XY: 726982

African (AFR) AF: 0.167 AC: 5591 AN: 33474

American (AMR) AF: 0.343 AC: 15319 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9099 AN: 26126

East Asian (EAS) AF: 0.584 AC: 23186 AN: 39696

South Asian (SAS) AF: 0.267 AC: 23053 AN: 86234

European-Finnish (FIN) AF: 0.279 AC: 14895 AN: 53420

Middle Eastern (MID) AF: 0.329 AC: 1897 AN: 5764

European-Non Finnish (NFE) AF: 0.293 AC: 325688 AN: 1111428

Other (OTH) AF: 0.306 AC: 18496 AN: 60376

GnomAD4 genome AF: 0.276 AC: 41881 AN: 151988 Hom.: 6152 Cov.: 32 AF XY: 0.279 AC XY: 20745 AN XY: 74298

African (AFR) AF: 0.180 AC: 7442 AN: 41454

American (AMR) AF: 0.332 AC: 5071 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3466

East Asian (EAS) AF: 0.581 AC: 2997 AN: 5162

South Asian (SAS) AF: 0.283 AC: 1359 AN: 4808

European-Finnish (FIN) AF: 0.270 AC: 2849 AN: 10554

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

European-Non Finnish (NFE) AF: 0.293 AC: 19895 AN: 67942

Other (OTH) AF: 0.297 AC: 627 AN: 2108

Alfa AF: 0.285 Hom.: 4671

Bravo AF: 0.280

Asia WGS AF: 0.383 AC: 1332 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	-0.80
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13170062; hg19: chr5-13882958; COSMIC: COSV54228739;