5-13841918-CAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr5-13841918-C-CAAA
• rs35337694
• NM_001369.3:c.5272-17_5272-15dupTTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001369.3(DNAH5):​c.5272-17_5272-15dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.617

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00802 (839/104582) while in subpopulation AFR AF= 0.0278 (783/28116). AF 95% confidence interval is 0.0262. There are 12 homozygotes in gnomad4. There are 396 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5272-17_5272-15dupTTT		intron_variant	Intron 32 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.5272-15_5272-14insTTT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5227-15_5227-14insTTT		intron_variant	Intron 32 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.00801 AC: 838 AN: 104588 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00319

Gnomad SAS AF: 0.000371

Gnomad FIN AF: 0.000529

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000274

Gnomad OTH AF: 0.00360

GnomAD4 exome AF: 0.00192 AC: 937 AN: 487352 Hom.: 0 Cov.: 0 AF XY: 0.00194 AC XY: 512 AN XY: 263412

Gnomad4 AFR exome AF: 0.00640

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00101

Gnomad4 EAS exome AF: 0.00551

Gnomad4 SAS exome AF: 0.00347

Gnomad4 FIN exome AF: 0.00232

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome AF: 0.00802 AC: 839 AN: 104582 Hom.: 12 Cov.: 0 AF XY: 0.00838 AC XY: 396 AN XY: 47228

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.00276

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00320

Gnomad4 SAS AF: 0.000371

Gnomad4 FIN AF: 0.000529

Gnomad4 NFE AF: 0.000274

Gnomad4 OTH AF: 0.00359

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35337694; hg19: chr5-13842027;