NM_001369.3:c.2578-36A>T

Variant names:

• chr5-13886165-T-A
• rs199959119
• NM_001369.3:c.2578-36A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001369.3(DNAH5):​c.2578-36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000727 in 1,530,352 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (3 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.05
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-13886165-T-A is Benign according to our data. Variant chr5-13886165-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 258013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000711 (985/1384790) while in subpopulation MID AF = 0.0107 (55/5160). AF 95% confidence interval is 0.00841. There are 3 homozygotes in GnomAdExome4. There are 515 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.2578-36A>T		intron	N/A	NP_001360.1
	DNAH5-AS1	NR_199035.1		n.118-10424T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2578-36A>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.2533-36A>T		intron	N/A	ENSP00000505288.1
	ENSG00000251423	ENST00000503244.2	TSL:4	n.254-10424T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000879 AC: 128 AN: 145546 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000873

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000642

Gnomad FIN AF: 0.000244

Gnomad MID AF: 0.0164

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.00297

GnomAD2 exomes AF: 0.000875 AC: 157 AN: 179332 AF XY: 0.000925

Gnomad AFR exome AF: 0.000170

Gnomad AMR exome AF: 0.000922

Gnomad ASJ exome AF: 0.000792

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000457

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.000711 AC: 985 AN: 1384790 Hom.: 3 Cov.: 29 AF XY: 0.000749 AC XY: 515 AN XY: 687884

African (AFR) AF: 0.000288 AC: 9 AN: 31296

American (AMR) AF: 0.000680 AC: 26 AN: 38220

Ashkenazi Jewish (ASJ) AF: 0.000793 AC: 20 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 37648

South Asian (SAS) AF: 0.000493 AC: 40 AN: 81128

European-Finnish (FIN) AF: 0.000202 AC: 8 AN: 39668

Middle Eastern (MID) AF: 0.0107 AC: 55 AN: 5160

European-Non Finnish (NFE) AF: 0.000715 AC: 764 AN: 1068790

Other (OTH) AF: 0.00109 AC: 63 AN: 57668

GnomAD4 genome AF: 0.000872 AC: 127 AN: 145562 Hom.: 0 Cov.: 32 AF XY: 0.000880 AC XY: 62 AN XY: 70482

African (AFR) AF: 0.000176 AC: 7 AN: 39676

American (AMR) AF: 0.00164 AC: 24 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.000873 AC: 3 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4974

South Asian (SAS) AF: 0.000646 AC: 3 AN: 4646

European-Finnish (FIN) AF: 0.000244 AC: 2 AN: 8212

Middle Eastern (MID) AF: 0.0144 AC: 4 AN: 278

European-Non Finnish (NFE) AF: 0.00117 AC: 78 AN: 66756

Other (OTH) AF: 0.00296 AC: 6 AN: 2030

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.000910

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs199959119; hg19: chr5-13886274;