chr5-13690482-G-A

Variant names:

• chr5-13690482-G-A
• rs144265705
• NM_001369.3:c.*1502C>T

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.*1502C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00938 in 152,280 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (11 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.378
• Publications: 1 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.87).
• BP6: Variant 5-13690482-G-A is Benign according to our data. Variant chr5-13690482-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 350904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00938 (1428/152280) while in subpopulation EAS AF = 0.045 (233/5178). AF 95% confidence interval is 0.0403. There are 11 homozygotes in GnomAd4. There are 701 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.*1502C>T		3_prime_UTR	Exon 79 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.*1502C>T		3_prime_UTR	Exon 79 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.*1502C>T		3_prime_UTR	Exon 79 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683611.1		n.2710C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00940 AC: 1430 AN: 152162 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00908

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00938 AC: 1428 AN: 152280 Hom.: 11 Cov.: 32 AF XY: 0.00942 AC XY: 701 AN XY: 74442

African (AFR) AF: 0.00325 AC: 135 AN: 41562

American (AMR) AF: 0.00431 AC: 66 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3468

East Asian (EAS) AF: 0.0450 AC: 233 AN: 5178

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4822

European-Finnish (FIN) AF: 0.00679 AC: 72 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0108 AC: 738 AN: 68036

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00860 Hom.: 0

Bravo AF: 0.00882

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		0.38
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: rs144265705; hg19: chr5-13690591;