Variant rs10931715 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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, single submitter B:1

Conservation

PhyloP100: 4.98

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 -14 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 id is 402755.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
DNAH7	NM_018897.3 linkuse as main transcript	c.1633C>T	p.Arg545Cys	missense_variant	14/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.1633C>T	p.Arg545Cys	missense_variant	14/65	1	NM_018897.3	P1	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

GnomAD3 exomes

AF:

0.636

AC:

143002

AN:

225008

Hom.:

46851

AF XY:

0.643

AC XY:

78843

AN XY:

122666

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 SAS exome

AF:

0.712

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

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.647

Gnomad4 ASJ exome

AF:

0.593

Gnomad4 EAS exome

AF:

0.687

Gnomad4 SAS exome

AF:

0.708

Gnomad4 FIN exome

AF:

0.672

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.626

GnomAD4 genome

AF:

0.541

AC:

82137

AN:

151944

Hom.:

24843

Cov.:

AF XY:

0.545

AC XY:

40449

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.587

Gnomad4 EAS

AF:

0.654

Gnomad4 SAS

AF:

0.725

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.661

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.633

Hom.:

75249

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

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

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

MutationTaster

Benign

7.4e-7

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

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

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