5-13884851-A-T

Variant names:

• chr5-13884851-A-T
• rs10866504
• NM_001369.3:c.2983+138T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369.3(DNAH5):​c.2983+138T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,356,056 control chromosomes in the GnomAD database, including 128,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14776 hom., cov: 33)
  • Exomes 𝑓: 0.43 (114200 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.160
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-13884851-A-T is Benign according to our data. Variant chr5-13884851-A-T is described in ClinVar as Benign. ClinVar VariationId is 1238691.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2983+138T>A		intron_variant	Intron 19 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2983+138T>A		intron_variant	Intron 19 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2938+138T>A		intron_variant	Intron 19 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-11738A>T		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.214-11738A>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66561 AN: 151978 Hom.: 14769 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.431 AC: 519226 AN: 1203960 Hom.: 114200 AF XY: 0.429 AC XY: 257340 AN XY: 600132

African (AFR) AF: 0.435 AC: 11245 AN: 25866

American (AMR) AF: 0.408 AC: 10651 AN: 26132

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 9233 AN: 21814

East Asian (EAS) AF: 0.735 AC: 24563 AN: 33418

South Asian (SAS) AF: 0.347 AC: 22189 AN: 63878

European-Finnish (FIN) AF: 0.450 AC: 17027 AN: 37832

Middle Eastern (MID) AF: 0.416 AC: 1429 AN: 3434

European-Non Finnish (NFE) AF: 0.426 AC: 400842 AN: 941324

Other (OTH) AF: 0.439 AC: 22047 AN: 50262

GnomAD4 genome AF: 0.438 AC: 66599 AN: 152096 Hom.: 14776 Cov.: 33 AF XY: 0.438 AC XY: 32579 AN XY: 74354

African (AFR) AF: 0.439 AC: 18221 AN: 41510

American (AMR) AF: 0.418 AC: 6390 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3757 AN: 5174

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4814

European-Finnish (FIN) AF: 0.441 AC: 4664 AN: 10564

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28916 AN: 67978

Other (OTH) AF: 0.440 AC: 928 AN: 2110

Alfa AF: 0.413 Hom.: 1582

Bravo AF: 0.438

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.26
PhyloP100		-0.16
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: rs10866504; hg19: chr5-13884960;