rs150679902

chr5-13911543-C-T

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.148

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.1537-50G>A		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.1537-50G>A		intron_variant		1	NM_001369.3	P4

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

GnomAD3 exomes AF: 0.0166 AC: 3696 AN: 222856 Hom.: 43 AF XY: 0.0171 AC XY: 2079 AN XY: 121792

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 SAS exome AF: 0.00764

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

Gnomad4 AFR exome AF: 0.00456

Gnomad4 AMR exome AF: 0.00917

Gnomad4 ASJ exome AF: 0.0213

Gnomad4 EAS exome AF: 0.0000558

Gnomad4 SAS exome AF: 0.00729

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.0279

Gnomad4 OTH exome AF: 0.0220

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

Gnomad4 AFR AF: 0.00537

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0209

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.37
Dann	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs150679902; hg19: chr5-13911652;