5-13911543-C-T

Variant names:

• chr5-13911543-C-T
• rs150679902
• NM_001369.3:c.1537-50G>A

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.1537-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,399,426 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (30 hom., cov: 32)
  • Exomes 𝑓: 0.024 (397 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.148
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-13911543-C-T is Benign according to our data. Variant chr5-13911543-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.017 (2584/152072) while in subpopulation NFE AF = 0.0266 (1811/67980). AF 95% confidence interval is 0.0256. There are 30 homozygotes in GnomAd4. There are 1196 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.1537-50G>A		intron_variant	Intron 11 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.1537-50G>A		intron_variant	Intron 11 of 78	1	NM_001369.3	ENSP00000265104.4

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2585 AN: 151954 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00539

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0166 AC: 3696 AN: 222856 AF XY: 0.0171

Gnomad AFR exome AF: 0.00482

Gnomad AMR exome AF: 0.00910

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.0000668

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0237 AC: 29515 AN: 1247354 Hom.: 397 Cov.: 17 AF XY: 0.0234 AC XY: 14745 AN XY: 630836

African (AFR) AF: 0.00456 AC: 128 AN: 28096

American (AMR) AF: 0.00917 AC: 403 AN: 43936

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 529 AN: 24872

East Asian (EAS) AF: 0.0000558 AC: 2 AN: 35856

South Asian (SAS) AF: 0.00729 AC: 583 AN: 79960

European-Finnish (FIN) AF: 0.0160 AC: 775 AN: 48374

Middle Eastern (MID) AF: 0.00737 AC: 37 AN: 5020

European-Non Finnish (NFE) AF: 0.0279 AC: 25895 AN: 928288

Other (OTH) AF: 0.0220 AC: 1163 AN: 52952

GnomAD4 genome AF: 0.0170 AC: 2584 AN: 152072 Hom.: 30 Cov.: 32 AF XY: 0.0161 AC XY: 1196 AN XY: 74342

African (AFR) AF: 0.00537 AC: 223 AN: 41498

American (AMR) AF: 0.0142 AC: 216 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4818

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10546

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1811 AN: 67980

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.0201 Hom.: 6

Bravo AF: 0.0166

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 11, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely 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	-0.84
CADD	Benign	0.37
DANN	Benign	0.17
PhyloP100		-0.15
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: rs150679902; hg19: chr5-13911652;