17-7797394-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020877.5(DNAH2):c.7950-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,764 control chromosomes in the GnomAD database, including 307,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23875 hom., cov: 31)

Exomes 𝑓: 0.62 ( 283839 hom. )

Consequence

DNAH2
NM_020877.5 splice_region, intron

Scores

Splicing: ADA: 0.0001956

Clinical Significance

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

Conservation

PhyloP100: 1.01

Publications

17 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-7797394-C-T is Benign according to our data. Variant chr17-7797394-C-T is described in ClinVar as Benign. ClinVar VariationId is 402710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.7950-6C>T		splice_region_variant, intron_variant	Intron 51 of 85	ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6 link	c.7950-6C>T		splice_region_variant, intron_variant	Intron 51 of 85	2	NM_020877.5	ENSP00000458355.1
DNAH2	ENST00000389173.6 link	c.7950-6C>T		splice_region_variant, intron_variant	Intron 50 of 84	2		ENSP00000373825.2

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82263

AN:

151872

Hom.:

23865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.558

GnomAD2 exomes

AF:

0.612

AC:

153822

AN:

251384

AF XY:

0.613

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.586

Gnomad EAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.622

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.620

AC:

906534

AN:

1461774

Hom.:

283839

Cov.:

AF XY:

0.620

AC XY:

450713

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.304

AC:

10164

AN:

33480

American (AMR)

AF:

0.696

AC:

31142

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

15175

AN:

26134

East Asian (EAS)

AF:

0.604

AC:

23995

AN:

39700

South Asian (SAS)

AF:

0.614

AC:

53003

AN:

86254

European-Finnish (FIN)

AF:

0.645

AC:

34401

AN:

53370

Middle Eastern (MID)

AF:

0.490

AC:

2826

AN:

5768

European-Non Finnish (NFE)

AF:

0.629

AC:

699282

AN:

1111954

Other (OTH)

AF:

0.605

AC:

36546

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

20384

40767

61151

81534

101918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18604

37208

55812

74416

93020

<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:

0.541

AC:

82294

AN:

151990

Hom.:

23875

Cov.:

AF XY:

0.548

AC XY:

40665

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.315

AC:

13060

AN:

41456

American (AMR)

AF:

0.635

AC:

9693

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2036

AN:

3464

East Asian (EAS)

AF:

0.625

AC:

3233

AN:

5170

South Asian (SAS)

AF:

0.619

AC:

2983

AN:

4818

European-Finnish (FIN)

AF:

0.646

AC:

6813

AN:

10546

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42545

AN:

67970

Other (OTH)

AF:

0.557

AC:

1172

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1742

3483

5225

6966

8708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.586

Hom.:

42824

Bravo

AF:

0.532

Asia WGS

AF:

0.618

AC:

2146

AN:

3478

EpiCase

AF:

0.608

EpiControl

AF:

0.607

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

-0.74

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

1.0

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -8

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