rs114621989

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018897.3(DNAH7):c.11947C>T(p.Arg3983Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00898 in 1,613,950 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0072 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 90 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:3

Conservation

PhyloP100: 2.35

Publications

13 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: ClinGen, 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:

LOC107985972 (HGNC:):

LOC107985972 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014028847).

BP6

Variant 2-195738049-G-A is Benign according to our data. Variant chr2-195738049-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 599650.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00715 (1089/152276) while in subpopulation NFE AF = 0.0105 (712/68024). AF 95% confidence interval is 0.00983. There are 4 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.11947C>T	p.Arg3983Trp	missense	Exon 65 of 65	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.11947C>T	p.Arg3983Trp	missense	Exon 65 of 65	ENSP00000311273.6	Q8WXX0-1
DNAH7	ENST00000409063.5	TSL:1	c.1396C>T	p.Arg466Trp	missense	Exon 10 of 10	ENSP00000386912.1	Q8WXX0-2
DNAH7	ENST00000438565.1	TSL:3	c.*78C>T		3_prime_UTR	Exon 3 of 3	ENSP00000409732.1	H7C362

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1090

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00830

AC:

2069

AN:

249300

AF XY:

0.00875

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00917

AC:

13406

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6632

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

33476

American (AMR)

AF:

0.00412

AC:

184

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

114

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39688

South Asian (SAS)

AF:

0.00767

AC:

662

AN:

86256

European-Finnish (FIN)

AF:

0.0136

AC:

729

AN:

53416

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0100

AC:

11163

AN:

1111842

Other (OTH)

AF:

0.00780

AC:

471

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

729

1458

2188

2917

3646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.00715

AC:

1089

AN:

152276

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41560

American (AMR)

AF:

0.00582

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00580

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0125

AC:

133

AN:

10598

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0105

AC:

712

AN:

68024

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00916

Hom.:

Bravo

AF:

0.00632

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00181

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00866

AC:

1047

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0104

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Male infertility with azoospermia or oligozoospermia due to single gene mutation (1)

Primary ciliary dyskinesia;C0037221:Abdominal situs inversus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.75

LIST_S2

Pathogenic

1.0

MetaRNN

Benign

0.014

MetaSVM

Uncertain

-0.066

MutationAssessor

Pathogenic

4.7

PhyloP100

2.4

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MVP

0.48

MPC

0.24

ClinPred

0.12

GERP RS

3.6

Varity_R

0.86

gMVP

0.91

Mutation Taster

=79/21

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over