rs1910089

Variant names:

• chr5-13841943-A-T
• rs1910089
• NM_001369.3:c.5272-39T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-13841943-A-T
• chr5-13841943-A-C

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.5272-39T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,053,576 control chromosomes in the GnomAD database, including 67,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8932 hom., cov: 25)
  • Exomes 𝑓: 0.33 (58647 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.546
• Publications: 1 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=-0.68).
• BP6: Variant 5-13841943-A-T is Benign according to our data. Variant chr5-13841943-A-T is described in ClinVar as Benign. ClinVar VariationId is 258044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 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.5272-39T>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.5272-39T>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.5227-39T>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.345 AC: 49277 AN: 142972 Hom.: 8931 Cov.: 25

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.262

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.368 AC: 73539 AN: 199882 AF XY: 0.365

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.640

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.327 AC: 297965 AN: 910508 Hom.: 58647 Cov.: 13 AF XY: 0.330 AC XY: 156055 AN XY: 473528

African (AFR) AF: 0.299 AC: 6362 AN: 21260

American (AMR) AF: 0.357 AC: 12313 AN: 34448

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 7093 AN: 21520

East Asian (EAS) AF: 0.557 AC: 20131 AN: 36124

South Asian (SAS) AF: 0.329 AC: 22112 AN: 67298

European-Finnish (FIN) AF: 0.324 AC: 14429 AN: 44486

Middle Eastern (MID) AF: 0.260 AC: 1048 AN: 4030

European-Non Finnish (NFE) AF: 0.313 AC: 200510 AN: 639834

Other (OTH) AF: 0.336 AC: 13967 AN: 41508

GnomAD4 genome AF: 0.345 AC: 49287 AN: 143068 Hom.: 8932 Cov.: 25 AF XY: 0.341 AC XY: 23487 AN XY: 68846

African (AFR) AF: 0.312 AC: 12147 AN: 38890

American (AMR) AF: 0.344 AC: 4883 AN: 14188

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1183 AN: 3428

East Asian (EAS) AF: 0.609 AC: 2945 AN: 4836

South Asian (SAS) AF: 0.343 AC: 1537 AN: 4484

European-Finnish (FIN) AF: 0.266 AC: 2047 AN: 7698

Middle Eastern (MID) AF: 0.272 AC: 74 AN: 272

European-Non Finnish (NFE) AF: 0.352 AC: 23392 AN: 66390

Other (OTH) AF: 0.354 AC: 708 AN: 1998

Alfa AF: 0.352 Hom.: 901

Bravo AF: 0.354

Asia WGS AF: 0.410 AC: 1358 AN: 3320

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	-0.68
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		-0.55
Mutation Taster		=27/73	disease causing (long InDel)

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: rs1910089; hg19: chr5-13842052;