rs10057007

Variant names:

• chr5-13882732-A-G
• rs10057007
• NM_001369.3:c.3258T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-13882732-A-G
• chr5-13882732-A-C

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.3258T>C​(p.Leu1086Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,608,472 control chromosomes in the GnomAD database, including 50,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5340 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44671 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.268
• Publications: 8 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

DNAH5-AS1 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-13882732-A-G is Benign according to our data. Variant chr5-13882732-A-G is described in ClinVar as Benign. ClinVar VariationId is 163154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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.3258T>C	p.Leu1086Leu	synonymous	Exon 21 of 79	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-13857A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.3258T>C	p.Leu1086Leu	synonymous	Exon 21 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.3213T>C	p.Leu1071Leu	synonymous	Exon 21 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-13857A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39386 AN: 151976 Hom.: 5337 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.253 AC: 63507 AN: 250522 AF XY: 0.250

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.244 AC: 355671 AN: 1456376 Hom.: 44671 Cov.: 31 AF XY: 0.244 AC XY: 177177 AN XY: 724798

African (AFR) AF: 0.310 AC: 10341 AN: 33380

American (AMR) AF: 0.331 AC: 14779 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7440 AN: 26086

East Asian (EAS) AF: 0.0974 AC: 3862 AN: 39664

South Asian (SAS) AF: 0.251 AC: 21629 AN: 86096

European-Finnish (FIN) AF: 0.236 AC: 12586 AN: 53266

Middle Eastern (MID) AF: 0.288 AC: 1656 AN: 5756

European-Non Finnish (NFE) AF: 0.243 AC: 268582 AN: 1107226

Other (OTH) AF: 0.246 AC: 14796 AN: 60210

GnomAD4 genome AF: 0.259 AC: 39404 AN: 152096 Hom.: 5340 Cov.: 32 AF XY: 0.259 AC XY: 19271 AN XY: 74356

African (AFR) AF: 0.307 AC: 12752 AN: 41506

American (AMR) AF: 0.280 AC: 4276 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 990 AN: 3462

East Asian (EAS) AF: 0.117 AC: 610 AN: 5192

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2530 AN: 10578

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16256 AN: 67954

Other (OTH) AF: 0.235 AC: 496 AN: 2110

Alfa AF: 0.246 Hom.: 7412

Bravo AF: 0.266

Asia WGS AF: 0.200 AC: 697 AN: 3478

EpiCase AF: 0.243

EpiControl AF: 0.249

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 3 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.8
DANN	Benign	0.86
PhyloP100		0.27
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: rs10057007; hg19: chr5-13882841;