rs144390858

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_StrongBS1BS2

The NM_018897.3(DNAH7):c.1139T>G(p.Met380Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,592,638 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 8.14

Publications

9 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:

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=0.011102408).

BP6

Variant 2-196001709-A-C is Benign according to our data. Variant chr2-196001709-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00894 (1361/152312) while in subpopulation NFE AF = 0.0136 (924/68028). AF 95% confidence interval is 0.0129. There are 5 homozygotes in GnomAd4. There are 609 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 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.1139T>G	p.Met380Arg	missense	Exon 11 of 65	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.1139T>G	p.Met380Arg	missense	Exon 11 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000410072.5	TSL:2	c.1139T>G	p.Met380Arg	missense	Exon 11 of 13	ENSP00000386260.1	Q8WXX0-4

Frequencies

GnomAD3 genomes

AF:

0.00896

AC:

1363

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00726

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00925

AC:

2176

AN:

235326

AF XY:

0.00931

show subpopulations

Gnomad AFR exome

AF:

0.000935

Gnomad AMR exome

AF:

0.00857

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00734

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0114

AC:

16396

AN:

1440326

Hom.:

121

Cov.:

AF XY:

0.0112

AC XY:

8022

AN XY:

714980

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

32732

American (AMR)

AF:

0.00861

AC:

358

AN:

41566

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

303

AN:

25536

East Asian (EAS)

AF:

0.00

AC:

AN:

39070

South Asian (SAS)

AF:

0.00395

AC:

320

AN:

81052

European-Finnish (FIN)

AF:

0.00841

AC:

447

AN:

53122

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0128

AC:

14097

AN:

1102066

Other (OTH)

AF:

0.0126

AC:

752

AN:

59494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

740

1481

2221

2962

3702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.00894

AC:

1361

AN:

152312

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

609

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41564

American (AMR)

AF:

0.0112

AC:

172

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00435

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00726

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0136

AC:

924

AN:

68028

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0113

Hom.:

Bravo

AF:

0.00869

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0137

AC:

113

ExAC

AF:

0.00900

AC:

1088

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

DNAH7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

8.1

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.90

Vest4

0.87

MVP

0.33

MPC

0.075

ClinPred

0.064

GERP RS

5.7

Varity_R

0.91

gMVP

0.85

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over