rs10078391

Variant names:

• chr5-13811666-T-C
• rs10078391
• NM_001369.3:c.7388A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-13811666-T-C
• chr5-13811666-T-G
• chr5-13811666-T-A

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.7388A>G​(p.Gln2463Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,613,578 control chromosomes in the GnomAD database, including 38,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q2463P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3556 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34597 hom.)
• Consequence: DNAH5 NM_001369.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 7.95
• Publications: 23 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 (MetaRNN=0.0016318262).
• BP6: Variant 5-13811666-T-C is Benign according to our data. Variant chr5-13811666-T-C is described in ClinVar as Benign. ClinVar VariationId is 163142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 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.7388A>G	p.Gln2463Arg	missense	Exon 44 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.7388A>G	p.Gln2463Arg	missense	Exon 44 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.7343A>G	p.Gln2448Arg	missense	Exon 44 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31767 AN: 152008 Hom.: 3559 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.214 AC: 53917 AN: 251392 AF XY: 0.211

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.210 AC: 306496 AN: 1461452 Hom.: 34597 Cov.: 33 AF XY: 0.208 AC XY: 151163 AN XY: 727056

African (AFR) AF: 0.195 AC: 6510 AN: 33468

American (AMR) AF: 0.162 AC: 7252 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3875 AN: 26126

East Asian (EAS) AF: 0.499 AC: 19787 AN: 39680

South Asian (SAS) AF: 0.158 AC: 13591 AN: 86244

European-Finnish (FIN) AF: 0.196 AC: 10494 AN: 53416

Middle Eastern (MID) AF: 0.120 AC: 694 AN: 5766

European-Non Finnish (NFE) AF: 0.208 AC: 231732 AN: 1111656

Other (OTH) AF: 0.208 AC: 12561 AN: 60380

GnomAD4 genome AF: 0.209 AC: 31780 AN: 152126 Hom.: 3556 Cov.: 32 AF XY: 0.206 AC XY: 15345 AN XY: 74368

African (AFR) AF: 0.195 AC: 8097 AN: 41512

American (AMR) AF: 0.170 AC: 2603 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2775 AN: 5156

South Asian (SAS) AF: 0.178 AC: 856 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10580

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14100 AN: 67994

Other (OTH) AF: 0.211 AC: 446 AN: 2110

Alfa AF: 0.209 Hom.: 10204

Bravo AF: 0.212

TwinsUK AF: 0.219 AC: 813

ALSPAC AF: 0.211 AC: 813

ESP6500AA AF: 0.202 AC: 888

ESP6500EA AF: 0.205 AC: 1761

ExAC AF: 0.215 AC: 26091

Asia WGS AF: 0.307 AC: 1065 AN: 3478

EpiCase AF: 0.200

EpiControl AF: 0.202

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.017	D
Polyphen		0.39	B
Vest4		0.29
MPC		0.10
ClinPred		0.042	T
GERP RS		5.8
Varity_R		0.35
gMVP		0.62
Mutation Taster		=49/51	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: rs10078391; hg19: chr5-13811775; COSMIC: COSV54215118; COSMIC: COSV54215118;