chr17-7778094-C-G

Variant names:

Variant summary

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

The NM_020877.5(DNAH2):c.5265C>G(p.Val1755Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,613,820 control chromosomes in the GnomAD database, including 672,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 52302 hom., cov: 31)

Exomes 𝑓: 0.92 ( 620501 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0290

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-7778094-C-G is Benign according to our data. Variant chr17-7778094-C-G is described in ClinVar as Benign. ClinVar VariationId is 402709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.029 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.5265C>G	p.Val1755Val	synonymous_variant	Exon 34 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.5265C>G	p.Val1755Val	synonymous_variant	Exon 34 of 86	2	NM_020877.5	ENSP00000458355.1	Q9P225-1
DNAH2	ENST00000389173.6 link	c.5265C>G	p.Val1755Val	synonymous_variant	Exon 33 of 85	2		ENSP00000373825.2	Q9P225-1
DNAH2	ENST00000574518.1 link	n.*1641C>G		non_coding_transcript_exon_variant	Exon 15 of 22	2		ENSP00000461273.1	I3L4H9
DNAH2	ENST00000574518.1 link	n.*1641C>G		3_prime_UTR_variant	Exon 15 of 22	2		ENSP00000461273.1	I3L4H9

Frequencies

GnomAD3 genomes

AF:

0.806

AC:

122591

AN:

152006

Hom.:

52282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.922

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.940

Gnomad OTH

AF:

0.820

GnomAD2 exomes

AF:

0.881

AC:

221642

AN:

251442

AF XY:

0.888

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.871

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.801

Gnomad FIN exome

AF:

0.967

Gnomad NFE exome

AF:

0.937

Gnomad OTH exome

AF:

0.903

GnomAD4 exome

AF:

0.918

AC:

1342151

AN:

1461696

Hom.:

620501

Cov.:

AF XY:

0.918

AC XY:

667388

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.492

AC:

16459

AN:

33472

American (AMR)

AF:

0.872

AC:

39014

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

23757

AN:

26136

East Asian (EAS)

AF:

0.798

AC:

31673

AN:

39698

South Asian (SAS)

AF:

0.865

AC:

74617

AN:

86246

European-Finnish (FIN)

AF:

0.967

AC:

51637

AN:

53418

Middle Eastern (MID)

AF:

0.822

AC:

4742

AN:

5768

European-Non Finnish (NFE)

AF:

0.941

AC:

1046376

AN:

1111840

Other (OTH)

AF:

0.892

AC:

53876

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

5224

10447

15671

20894

26118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21502

43004

64506

86008

107510

<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:

0.806

AC:

122657

AN:

152124

Hom.:

52302

Cov.:

AF XY:

0.811

AC XY:

60306

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.506

AC:

20951

AN:

41444

American (AMR)

AF:

0.861

AC:

13165

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.905

AC:

3141

AN:

3472

East Asian (EAS)

AF:

0.806

AC:

4172

AN:

5174

South Asian (SAS)

AF:

0.871

AC:

4198

AN:

4818

European-Finnish (FIN)

AF:

0.971

AC:

10301

AN:

10606

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.940

AC:

63917

AN:

68012

Other (OTH)

AF:

0.822

AC:

1735

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

907

1814

2722

3629

4536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.898

Hom.:

20250

Bravo

AF:

0.785

Asia WGS

AF:

0.849

AC:

2952

AN:

3478

EpiCase

AF:

0.935

EpiControl

AF:

0.929

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 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 -

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

-0.56

CADD

Benign

1.9

(source)

DANN

Benign

0.61

PhyloP100

0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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