5-13867994-TAA-TA

Variant names:

• chr5-13867994-TA-T
• rs35398031
• NM_001369.3:c.3835-3delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.3835-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12176 hom., cov: 0)
  • Exomes 𝑓: 0.43 (137623 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.454
• Publications: 8 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 -16 ACMG points.

• BP6: Variant 5-13867994-TA-T is Benign according to our data. Variant chr5-13867994-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 215494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 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.3835-3delT		splice_region intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.117+7448delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.3835-3delT		splice_region intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.3790-3delT		splice_region intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.253+7440delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59796 AN: 151382 Hom.: 12158 Cov.: 0

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.413 AC: 99007 AN: 239752 AF XY: 0.421

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.250

Gnomad FIN exome AF: 0.487

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.434 AC: 628653 AN: 1448288 Hom.: 137623 Cov.: 0 AF XY: 0.435 AC XY: 313552 AN XY: 720756

African (AFR) AF: 0.318 AC: 10521 AN: 33096

American (AMR) AF: 0.302 AC: 13360 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 9349 AN: 25924

East Asian (EAS) AF: 0.261 AC: 10272 AN: 39310

South Asian (SAS) AF: 0.469 AC: 40187 AN: 85720

European-Finnish (FIN) AF: 0.479 AC: 25435 AN: 53100

Middle Eastern (MID) AF: 0.349 AC: 1966 AN: 5634

European-Non Finnish (NFE) AF: 0.447 AC: 492577 AN: 1101508

Other (OTH) AF: 0.418 AC: 24986 AN: 59800

GnomAD4 genome AF: 0.395 AC: 59856 AN: 151498 Hom.: 12176 Cov.: 0 AF XY: 0.394 AC XY: 29155 AN XY: 73988

African (AFR) AF: 0.314 AC: 12941 AN: 41240

American (AMR) AF: 0.342 AC: 5199 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1237 AN: 3464

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5168

South Asian (SAS) AF: 0.464 AC: 2225 AN: 4794

European-Finnish (FIN) AF: 0.488 AC: 5122 AN: 10486

Middle Eastern (MID) AF: 0.371 AC: 106 AN: 286

European-Non Finnish (NFE) AF: 0.450 AC: 30537 AN: 67856

Other (OTH) AF: 0.405 AC: 850 AN: 2100

Alfa AF: 0.332 Hom.: 1450

Bravo AF: 0.374

Asia WGS AF: 0.381 AC: 1328 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35398031; hg19: chr5-13868103; COSMIC: COSV54209857;