rs62059684

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020877.5(DNAH2):c.5010G>A(p.Ala1670Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,612,050 control chromosomes in the GnomAD database, including 77,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5309 hom., cov: 31)

Exomes 𝑓: 0.30 ( 72385 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.137

Publications

9 publications found

Variant links:

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

DNAH2 Gene-Disease associations (from GenCC):

spermatogenic failure 45
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

DNAH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 17-7776841-G-A is Benign according to our data. Variant chr17-7776841-G-A is described in ClinVar as Benign. ClinVar VariationId is 402708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.137 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.5010G>A	p.Ala1670Ala	synonymous_variant	Exon 32 of 86	ENST00000572933.6	NP_065928.2	Q9P225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH2	ENST00000572933.6 link	c.5010G>A	p.Ala1670Ala	synonymous_variant	Exon 32 of 86	2	NM_020877.5	ENSP00000458355.1	Q9P225-1
DNAH2	ENST00000389173.6 link	c.5010G>A	p.Ala1670Ala	synonymous_variant	Exon 31 of 85	2		ENSP00000373825.2	Q9P225-1
DNAH2	ENST00000574518.1 link	n.*1386G>A		non_coding_transcript_exon_variant	Exon 13 of 22	2		ENSP00000461273.1	I3L4H9
DNAH2	ENST00000574518.1 link	n.*1386G>A		3_prime_UTR_variant	Exon 13 of 22	2		ENSP00000461273.1	I3L4H9

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34718

AN:

151948

Hom.:

5311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.241

AC:

60310

AN:

250516

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.0519

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.302

AC:

440227

AN:

1459984

Hom.:

72385

Cov.:

AF XY:

0.299

AC XY:

216983

AN XY:

726284

show subpopulations

African (AFR)

AF:

0.0460

AC:

1539

AN:

33444

American (AMR)

AF:

0.148

AC:

6603

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8695

AN:

26072

East Asian (EAS)

AF:

0.000605

AC:

AN:

39672

South Asian (SAS)

AF:

0.135

AC:

11617

AN:

86206

European-Finnish (FIN)

AF:

0.347

AC:

18475

AN:

53200

Middle Eastern (MID)

AF:

0.254

AC:

1464

AN:

5756

European-Non Finnish (NFE)

AF:

0.338

AC:

375541

AN:

1110734

Other (OTH)

AF:

0.270

AC:

16269

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15019

30038

45058

60077

75096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11636

23272

34908

46544

58180

<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:

0.228

AC:

34713

AN:

152066

Hom.:

5309

Cov.:

AF XY:

0.225

AC XY:

16687

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0569

AC:

2364

AN:

41518

American (AMR)

AF:

0.192

AC:

2924

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1164

AN:

3470

East Asian (EAS)

AF:

0.00232

AC:

AN:

5176

South Asian (SAS)

AF:

0.127

AC:

610

AN:

4820

European-Finnish (FIN)

AF:

0.349

AC:

3690

AN:

10566

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23074

AN:

67948

Other (OTH)

AF:

0.233

AC:

491

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1276

2552

3829

5105

6381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.292

Hom.:

6202

Bravo

AF:

0.209

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

EpiCase

AF:

0.335

EpiControl

AF:

0.335

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH2-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

1.3

(source)

DANN

Benign

0.83

PhyloP100

-0.14

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over