5-13901230-G-T

Variant names:

• chr5-13901230-G-T
• rs150480592
• NM_001369.3:c.2052+22C>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.2052+22C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,608,384 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (96 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0860
• 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=-0.85).
• BP6: Variant 5-13901230-G-T is Benign according to our data. Variant chr5-13901230-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258007.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 = 0.00643 (979/152318) while in subpopulation NFE AF = 0.0101 (687/68022). AF 95% confidence interval is 0.00947. There are 8 homozygotes in GnomAd4. There are 436 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2052+22C>A		intron_variant	Intron 14 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2052+22C>A		intron_variant	Intron 14 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2007+22C>A		intron_variant	Intron 14 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.*194G>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 979 AN: 152200 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00972

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00789 AC: 1951 AN: 247340 AF XY: 0.00826

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00616

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00990 AC: 14417 AN: 1456066 Hom.: 96 Cov.: 30 AF XY: 0.00988 AC XY: 7160 AN XY: 724626

African (AFR) AF: 0.00114 AC: 38 AN: 33432

American (AMR) AF: 0.00530 AC: 237 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00387 AC: 101 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39664

South Asian (SAS) AF: 0.0119 AC: 1028 AN: 86170

European-Finnish (FIN) AF: 0.00656 AC: 330 AN: 50290

Middle Eastern (MID) AF: 0.00920 AC: 53 AN: 5764

European-Non Finnish (NFE) AF: 0.0109 AC: 12100 AN: 1109650

Other (OTH) AF: 0.00876 AC: 528 AN: 60278

GnomAD4 genome AF: 0.00643 AC: 979 AN: 152318 Hom.: 8 Cov.: 33 AF XY: 0.00585 AC XY: 436 AN XY: 74490

African (AFR) AF: 0.00200 AC: 83 AN: 41576

American (AMR) AF: 0.00477 AC: 73 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4830

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 687 AN: 68022

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00783 Hom.: 1

Bravo AF: 0.00625

Asia WGS AF: 0.00375 AC: 13 AN: 3478

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

- -

Primary ciliary dyskinesia 3 Benign:1

Jun 15, 2021

Pars Genome Lab

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	-0.85
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism

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: rs150480592; hg19: chr5-13901339;