dbSNP rs75859635: DNAH7:p.Thr2114Ala (chr2-195873641-T-C) – ACMG Classification: Benign (-20 pts)

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.6340A>G(p.Thr2114Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0368 in 1,531,804 control chromosomes in the GnomAD database, including 1,169 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 94 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1075 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.91

Publications

6 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=0.007309526).

BP6

Variant 2-195873641-T-C is Benign according to our data. Variant chr2-195873641-T-C is described in ClinVar as Benign. ClinVar VariationId is 402749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3 link	c.6340A>G	p.Thr2114Ala	missense_variant	Exon 39 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.6340A>G	p.Thr2114Ala	missense_variant	Exon 39 of 65	1	NM_018897.3	ENSP00000311273.6		Q8WXX0-1

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4751

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0346

GnomAD2 exomes

AF:

0.0303

AC:

5804

AN:

191358

AF XY:

0.0317

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0321

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0339

Gnomad NFE exome

AF:

0.0407

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0374

AC:

51645

AN:

1379600

Hom.:

1075

Cov.:

AF XY:

0.0370

AC XY:

25347

AN XY:

685046

show subpopulations

African (AFR)

AF:

0.0168

AC:

482

AN:

28776

American (AMR)

AF:

0.0202

AC:

577

AN:

28626

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

760

AN:

24042

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35714

South Asian (SAS)

AF:

0.0161

AC:

1148

AN:

71282

European-Finnish (FIN)

AF:

0.0354

AC:

1857

AN:

52472

Middle Eastern (MID)

AF:

0.0646

AC:

358

AN:

5538

European-Non Finnish (NFE)

AF:

0.0413

AC:

44436

AN:

1076124

Other (OTH)

AF:

0.0355

AC:

2025

AN:

57026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

2152

4304

6457

8609

10761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1650

3300

4950

6600

8250

<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:

0.0312

AC:

4750

AN:

152204

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2263

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0167

AC:

696

AN:

41562

American (AMR)

AF:

0.0300

AC:

457

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0108

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0365

AC:

387

AN:

10610

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0427

AC:

2905

AN:

68018

Other (OTH)

AF:

0.0343

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

234

467

701

934

1168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0390

Hom.:

377

Bravo

AF:

0.0311

TwinsUK

AF:

0.0399

AC:

148

ALSPAC

AF:

0.0413

AC:

159

ESP6500AA

AF:

0.0144

AC:

ESP6500EA

AF:

0.0434

AC:

353

ExAC

AF:

0.0307

AC:

3712

Asia WGS

AF:

0.00780

AC:

AN:

3476

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

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.022

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

4.9

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Benign

0.41

Polyphen

0.019

Vest4

0.29

MPC

0.035

ClinPred

0.0069

GERP RS

4.8

Varity_R

0.35

gMVP

0.50

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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