17-7770610-C-G

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.4152C>G(p.Pro1384Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,714 control chromosomes in the GnomAD database, including 67,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7181 hom., cov: 31)

Exomes 𝑓: 0.28 ( 60263 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.31

Publications

14 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=-0.34).

BP6

Variant 17-7770610-C-G is Benign according to our data. Variant chr17-7770610-C-G is described in ClinVar as Benign. ClinVar VariationId is 402707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020877.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	NM_020877.5	MANE Select	c.4152C>G	p.Pro1384Pro	synonymous	Exon 26 of 86	NP_065928.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH2	ENST00000572933.6	TSL:2 MANE Select	c.4152C>G	p.Pro1384Pro	synonymous	Exon 26 of 86	ENSP00000458355.1
DNAH2	ENST00000389173.6	TSL:2	c.4152C>G	p.Pro1384Pro	synonymous	Exon 25 of 85	ENSP00000373825.2
DNAH2	ENST00000574518.1	TSL:2	n.*415C>G		non_coding_transcript_exon	Exon 8 of 22	ENSP00000461273.1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45947

AN:

151938

Hom.:

7174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.292

GnomAD2 exomes

AF:

0.324

AC:

81394

AN:

251408

AF XY:

0.319

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.492

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.408

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.282

AC:

411700

AN:

1461658

Hom.:

60263

Cov.:

AF XY:

0.283

AC XY:

205594

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.325

AC:

10889

AN:

33470

American (AMR)

AF:

0.482

AC:

21551

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

7203

AN:

26126

East Asian (EAS)

AF:

0.387

AC:

15355

AN:

39700

South Asian (SAS)

AF:

0.361

AC:

31174

AN:

86238

European-Finnish (FIN)

AF:

0.286

AC:

15284

AN:

53408

Middle Eastern (MID)

AF:

0.246

AC:

1418

AN:

5764

European-Non Finnish (NFE)

AF:

0.262

AC:

291165

AN:

1111842

Other (OTH)

AF:

0.292

AC:

17661

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16162

32324

48485

64647

80809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10122

20244

30366

40488

50610

<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:

0.302

AC:

45997

AN:

152056

Hom.:

7181

Cov.:

AF XY:

0.309

AC XY:

22978

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.323

AC:

13378

AN:

41470

American (AMR)

AF:

0.402

AC:

6132

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

974

AN:

3470

East Asian (EAS)

AF:

0.390

AC:

2017

AN:

5168

South Asian (SAS)

AF:

0.369

AC:

1778

AN:

4824

European-Finnish (FIN)

AF:

0.290

AC:

3071

AN:

10582

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17771

AN:

67960

Other (OTH)

AF:

0.293

AC:

618

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1613

3226

4839

6452

8065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.230

Hom.:

1339

Bravo

AF:

0.310

Asia WGS

AF:

0.391

AC:

1357

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.252

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 21, 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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.3

(source)

DANN

Benign

0.79

PhyloP100

1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over