5-13690936-T-C

Variant names:

• chr5-13690936-T-C
• rs2896111
• NM_001369.3:c.*1048A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.*1048A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,952 control chromosomes in the GnomAD database, including 18,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18870 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0750
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-13690936-T-C is Benign according to our data. Variant chr5-13690936-T-C is described in ClinVar as Benign. ClinVar VariationId is 350910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

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.*1048A>G		3_prime_UTR	Exon 79 of 79	NP_001360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.*1048A>G		3_prime_UTR	Exon 79 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.*1048A>G		3_prime_UTR	Exon 79 of 79	ENSP00000505288.1
	DNAH5	ENST00000683611.1		n.2256A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75005 AN: 151832 Hom.: 18864 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.507

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: 0.494 AC: 75051 AN: 151952 Hom.: 18870 Cov.: 32 AF XY: 0.490 AC XY: 36356 AN XY: 74262

African (AFR) AF: 0.419 AC: 17361 AN: 41440

American (AMR) AF: 0.502 AC: 7671 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1831 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2049 AN: 5182

South Asian (SAS) AF: 0.419 AC: 2013 AN: 4806

European-Finnish (FIN) AF: 0.537 AC: 5658 AN: 10534

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36740 AN: 67942

Other (OTH) AF: 0.508 AC: 1069 AN: 2106

Alfa AF: 0.501 Hom.: 3749

Bravo AF: 0.492

Asia WGS AF: 0.427 AC: 1483 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.82
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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: rs2896111; hg19: chr5-13691045;