rs6554812

Variant names:

• chr5-13762863-T-C
• rs6554812
• NM_001369.3:c.10140A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.10140A>G​(p.Glu3380Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,612,358 control chromosomes in the GnomAD database, including 68,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7746 hom., cov: 33)
  • Exomes 𝑓: 0.28 (60554 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.0450
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-13762863-T-C is Benign according to our data. Variant chr5-13762863-T-C is described in ClinVar as Benign. ClinVar VariationId is 163137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.045 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 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.10140A>G	p.Glu3380Glu	synonymous	Exon 60 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.10140A>G	p.Glu3380Glu	synonymous	Exon 60 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.10095A>G	p.Glu3365Glu	synonymous	Exon 60 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.648A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46838 AN: 152010 Hom.: 7726 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.298 AC: 74871 AN: 250966 AF XY: 0.302

Gnomad AFR exome AF: 0.367

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.0947

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.280 AC: 408259 AN: 1460230 Hom.: 60554 Cov.: 35 AF XY: 0.284 AC XY: 206515 AN XY: 726510

African (AFR) AF: 0.365 AC: 12206 AN: 33428

American (AMR) AF: 0.294 AC: 13167 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5437 AN: 26122

East Asian (EAS) AF: 0.104 AC: 4118 AN: 39684

South Asian (SAS) AF: 0.434 AC: 37420 AN: 86220

European-Finnish (FIN) AF: 0.411 AC: 21944 AN: 53372

Middle Eastern (MID) AF: 0.225 AC: 1294 AN: 5760

European-Non Finnish (NFE) AF: 0.267 AC: 296021 AN: 1110586

Other (OTH) AF: 0.276 AC: 16652 AN: 60340

GnomAD4 genome AF: 0.308 AC: 46909 AN: 152128 Hom.: 7746 Cov.: 33 AF XY: 0.315 AC XY: 23440 AN XY: 74368

African (AFR) AF: 0.368 AC: 15280 AN: 41494

American (AMR) AF: 0.269 AC: 4118 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3470

East Asian (EAS) AF: 0.113 AC: 587 AN: 5184

South Asian (SAS) AF: 0.441 AC: 2126 AN: 4822

European-Finnish (FIN) AF: 0.442 AC: 4673 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18600 AN: 67986

Other (OTH) AF: 0.286 AC: 602 AN: 2108

Alfa AF: 0.277 Hom.: 18497

Bravo AF: 0.291

Asia WGS AF: 0.329 AC: 1144 AN: 3478

EpiCase AF: 0.257

EpiControl AF: 0.257

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		0.045
Mutation Taster		=98/2	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: rs6554812; hg19: chr5-13762972; COSMIC: COSV54228724;