17-7770604-A-T

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.4146A>T(p.Ile1382Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,614,008 control chromosomes in the GnomAD database, including 1,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 277 hom., cov: 32)

Exomes 𝑓: 0.029 ( 963 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.573

Publications

6 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=-0.79).

BP6

Variant 17-7770604-A-T is Benign according to our data. Variant chr17-7770604-A-T is described in ClinVar as Benign. ClinVar VariationId is 402706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 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.4146A>T	p.Ile1382Ile	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.4146A>T	p.Ile1382Ile	synonymous	Exon 26 of 86	ENSP00000458355.1
DNAH2	ENST00000389173.6	TSL:2	c.4146A>T	p.Ile1382Ile	synonymous	Exon 25 of 85	ENSP00000373825.2
DNAH2	ENST00000574518.1	TSL:2	n.*409A>T		non_coding_transcript_exon	Exon 8 of 22	ENSP00000461273.1

Frequencies

GnomAD3 genomes

AF:

0.0489

AC:

7443

AN:

152102

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0524

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0517

GnomAD2 exomes

AF:

0.0341

AC:

8567

AN:

251438

AF XY:

0.0342

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0714

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0289

Gnomad OTH exome

AF:

0.0360

GnomAD4 exome

AF:

0.0294

AC:

42981

AN:

1461788

Hom.:

963

Cov.:

AF XY:

0.0302

AC XY:

21986

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.106

AC:

3553

AN:

33478

American (AMR)

AF:

0.0199

AC:

888

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0696

AC:

1819

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0495

AC:

4271

AN:

86242

European-Finnish (FIN)

AF:

0.0251

AC:

1342

AN:

53418

Middle Eastern (MID)

AF:

0.0876

AC:

505

AN:

5766

European-Non Finnish (NFE)

AF:

0.0257

AC:

28523

AN:

1111938

Other (OTH)

AF:

0.0344

AC:

2077

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

2192

4383

6575

8766

10958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1116

2232

3348

4464

5580

<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:

0.0490

AC:

7465

AN:

152220

Hom.:

277

Cov.:

AF XY:

0.0489

AC XY:

3642

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.101

AC:

4187

AN:

41510

American (AMR)

AF:

0.0337

AC:

515

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0523

AC:

252

AN:

4822

European-Finnish (FIN)

AF:

0.0263

AC:

279

AN:

10608

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1838

AN:

68016

Other (OTH)

AF:

0.0511

AC:

108

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

339

678

1018

1357

1696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0279

Hom.:

Bravo

AF:

0.0509

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0367

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH2-related disorder

Benign:1

Jan 24, 2020

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.4

(source)

DANN

Benign

0.78

PhyloP100

-0.57

Mutation Taster

=99/1

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