NM_018897.3:c.1139T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: 8.14

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 402759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-196001709-A-C is described in Lovd as [Benign]. Variant chr2-196001709-A-C is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3 link	c.1139T>G	p.Met380Arg	missense_variant	Exon 11 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.1139T>G	p.Met380Arg	missense_variant	Exon 11 of 65	1	NM_018897.3	ENSP00000311273.6		Q8WXX0-1
DNAH7	ENST00000410072.5 link	c.1139T>G	p.Met380Arg	missense_variant	Exon 11 of 13	2		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

GnomAD3 exomes

AF:

0.00925

AC:

2176

AN:

235326

Hom.:

AF XY:

0.00931

AC XY:

1189

AN XY:

127658

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 SAS exome

AF:

0.00394

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

Gnomad4 AFR exome

AF:

0.00171

Gnomad4 AMR exome

AF:

0.00861

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00395

Gnomad4 FIN exome

AF:

0.00841

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00894

AC:

1361

AN:

152312

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

609

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00726

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0119

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

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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 -

DNAH7-related disorder

Benign:1

Mar 02, 2020

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

.;D

Polyphen

0.90

P;.

Vest4

0.87

MVP

0.33

MPC

0.075

ClinPred

0.064

GERP RS

5.7

Varity_R

0.91

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over