rs34580014

Variant names:

• chr5-13913884-G-A
• rs34580014
• NM_001369.3:c.1395C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.1395C>T​(p.Ser465Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,613,478 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (183 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (158 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.16
• Publications: 3 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 5-13913884-G-A is Benign according to our data. Variant chr5-13913884-G-A is described in ClinVar as Benign. ClinVar VariationId is 226594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 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.1395C>T	p.Ser465Ser	synonymous	Exon 11 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.1395C>T	p.Ser465Ser	synonymous	Exon 11 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.1350C>T	p.Ser450Ser	synonymous	Exon 11 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000508040.1	TSL:2	n.1803C>T		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4004 AN: 151956 Hom.: 182 Cov.: 33

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00944

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00755 AC: 1895 AN: 250926 AF XY: 0.00582

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.00576

Gnomad ASJ exome AF: 0.00834

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000644

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00314 AC: 4587 AN: 1461404 Hom.: 158 Cov.: 34 AF XY: 0.00276 AC XY: 2008 AN XY: 727008

African (AFR) AF: 0.0970 AC: 3246 AN: 33462

American (AMR) AF: 0.00599 AC: 268 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00723 AC: 189 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.000394 AC: 34 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00729 AC: 42 AN: 5764

European-Non Finnish (NFE) AF: 0.000342 AC: 380 AN: 1111682

Other (OTH) AF: 0.00707 AC: 427 AN: 60364

GnomAD4 genome AF: 0.0264 AC: 4017 AN: 152074 Hom.: 183 Cov.: 33 AF XY: 0.0260 AC XY: 1933 AN XY: 74334

African (AFR) AF: 0.0910 AC: 3778 AN: 41498

American (AMR) AF: 0.00943 AC: 144 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 67920

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0126 Hom.: 36

Bravo AF: 0.0293

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.00119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Primary ciliary dyskinesia (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia 3 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.5
DANN	Benign	0.72
PhyloP100		1.2
Mutation Taster		=95/5	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: rs34580014; hg19: chr5-13913993;