rs16902967

Variant names:

• chr5-13957203-G-A
• rs16902967
• ENST00000681290.1:c.13-25959C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000681290.1(DNAH5):​c.13-25959C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 152,180 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.042 (155 hom., cov: 33)
• Consequence: DNAH5 ENST00000681290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	XM_005248262.4	c.166-25959C>T		intron_variant	Intron 1 of 78		XP_005248319.2
DNAH5	XM_017009177.2	c.166-25959C>T		intron_variant	Intron 1 of 76		XP_016864666.1
DNAH5	XM_017009180.2	c.166-25959C>T		intron_variant	Intron 1 of 73		XP_016864669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000681290.1	c.13-25959C>T		intron_variant	Intron 1 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6450 AN: 152062 Hom.: 155 Cov.: 33

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0424 AC: 6453 AN: 152180 Hom.: 155 Cov.: 33 AF XY: 0.0427 AC XY: 3179 AN XY: 74398

African (AFR) AF: 0.0657 AC: 2726 AN: 41500

American (AMR) AF: 0.0445 AC: 681 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 113 AN: 3472

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5182

South Asian (SAS) AF: 0.0465 AC: 224 AN: 4822

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0281 AC: 1910 AN: 67994

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0388 Hom.: 55

Bravo AF: 0.0419

Asia WGS AF: 0.0500 AC: 174 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16902967; hg19: chr5-13957312;