dbSNP rs61744054: DNAH5:p.Gly4236Gly (chr5-13716688-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369.3(DNAH5):c.12708T>C(p.Gly4236Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,609,210 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 126 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 163 hom. )

Consequence

DNAH5
NM_001369.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.35

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-13716688-A-G is Benign according to our data. Variant chr5-13716688-A-G is described in ClinVar as Benign. ClinVar VariationId is 226592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 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.12708T>C	p.Gly4236Gly	splice_region synonymous	Exon 74 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.12708T>C	p.Gly4236Gly	splice_region synonymous	Exon 74 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.12663T>C	p.Gly4221Gly	splice_region synonymous	Exon 74 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3663

AN:

152138

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00972

AC:

2434

AN:

250520

AF XY:

0.00871

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.00507

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00443

AC:

6448

AN:

1456954

Hom.:

163

Cov.:

AF XY:

0.00446

AC XY:

3233

AN XY:

725228

show subpopulations

African (AFR)

AF:

0.0830

AC:

2763

AN:

33304

American (AMR)

AF:

0.0114

AC:

510

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00506

AC:

132

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.0108

AC:

927

AN:

86098

European-Finnish (FIN)

AF:

0.0000752

AC:

AN:

53186

Middle Eastern (MID)

AF:

0.0304

AC:

175

AN:

5762

European-Non Finnish (NFE)

AF:

0.00125

AC:

1387

AN:

1107938

Other (OTH)

AF:

0.00913

AC:

550

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

307

614

922

1229

1536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0241

AC:

3668

AN:

152256

Hom.:

126

Cov.:

AF XY:

0.0242

AC XY:

1799

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0768

AC:

3188

AN:

41530

American (AMR)

AF:

0.0146

AC:

224

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00809

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00204

AC:

139

AN:

68020

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

173

347

520

694

867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0287

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00303

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

Primary ciliary dyskinesia 3 (3)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0080

(source)

DANN

Benign

0.45

PhyloP100

-3.4

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over