rs10931715

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_018897.3(DNAH7):c.1633C>T(p.Arg545Cys) variant causes a missense change. The variant allele was found at a frequency of 0.646 in 1,573,502 control chromosomes in the GnomAD database, including 336,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R545H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.54 ( 24843 hom., cov: 33)

Exomes 𝑓: 0.66 ( 311874 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.98

Publications

31 publications found

Variant links:

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 50
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

DNAH7 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 (MetaRNN=2.8779305E-6).

BP6

Variant 2-195987187-G-A is Benign according to our data. Variant chr2-195987187-G-A is described in ClinVar as Benign. ClinVar VariationId is 402755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3 link	c.1633C>T	p.Arg545Cys	missense_variant	Exon 14 of 65	ENST00000312428.11	NP_061720.2	Q8WXX0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11 link	c.1633C>T	p.Arg545Cys	missense_variant	Exon 14 of 65	1	NM_018897.3	ENSP00000311273.6		Q8WXX0-1

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82129

AN:

151826

Hom.:

24839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.724

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.543

GnomAD2 exomes

AF:

0.636

AC:

143002

AN:

225008

AF XY:

0.643

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.656

Gnomad ASJ exome

AF:

0.601

Gnomad EAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.660

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.657

AC:

934270

AN:

1421558

Hom.:

311874

Cov.:

AF XY:

0.659

AC XY:

465795

AN XY:

707012

show subpopulations

African (AFR)

AF:

0.217

AC:

6957

AN:

32068

American (AMR)

AF:

0.647

AC:

23999

AN:

37066

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

14897

AN:

25114

East Asian (EAS)

AF:

0.687

AC:

26550

AN:

38642

South Asian (SAS)

AF:

0.708

AC:

55706

AN:

78712

European-Finnish (FIN)

AF:

0.672

AC:

35452

AN:

52758

Middle Eastern (MID)

AF:

0.524

AC:

2959

AN:

5644

European-Non Finnish (NFE)

AF:

0.669

AC:

731039

AN:

1092876

Other (OTH)

AF:

0.626

AC:

36711

AN:

58678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

12792

25585

38377

51170

63962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18876

37752

56628

75504

94380

<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:

82137

AN:

151944

Hom.:

24843

Cov.:

AF XY:

0.545

AC XY:

40449

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.245

AC:

10158

AN:

41420

American (AMR)

AF:

0.598

AC:

9143

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2036

AN:

3468

East Asian (EAS)

AF:

0.654

AC:

3382

AN:

5174

South Asian (SAS)

AF:

0.725

AC:

3501

AN:

4832

European-Finnish (FIN)

AF:

0.672

AC:

7084

AN:

10546

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.661

AC:

44910

AN:

67910

Other (OTH)

AF:

0.540

AC:

1140

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1717

3435

5152

6870

8587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.619

Hom.:

99310

Bravo

AF:

0.519

TwinsUK

AF:

0.681

AC:

2526

ALSPAC

AF:

0.678

AC:

2614

ESP6500AA

AF:

0.259

AC:

934

ESP6500EA

AF:

0.644

AC:

5239

ExAC

AF:

0.627

AC:

75692

Asia WGS

AF:

0.659

AC:

2286

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 -

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

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

Eigen

Benign

-0.012

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0000029

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.7

PhyloP100

5.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.12

Sift

Benign

0.18

Polyphen

0.014

Vest4

0.58

MPC

0.036

ClinPred

0.059

GERP RS

4.9

Varity_R

0.24

gMVP

0.52

Mutation Taster

=98/2

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