Variant 2-195808809-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018897.3(DNAH7):c.9956T>C(p.Leu3319Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,613,984 control chromosomes in the GnomAD database, including 797,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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.

Frequency

Genomes: 𝑓 0.97 ( 71268 hom., cov: 32)

Exomes 𝑓: 1.0 ( 726017 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.58

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=6.7730775E-7).

BP6

Variant 2-195808809-A-G is Benign according to our data. Variant chr2-195808809-A-G is described in ClinVar as [Benign]. Clinvar id is 402748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.9956T>C	p.Leu3319Pro	missense_variant	53/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.9956T>C	p.Leu3319Pro	missense_variant	53/65	1	NM_018897.3	P1	Q8WXX0-1

Frequencies

GnomAD3 genomes

AF:

0.966

AC:

147013

AN:

152160

Hom.:

71225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.978

GnomAD3 exomes

AF:

0.991

AC:

247140

AN:

249300

Hom.:

122597

AF XY:

0.993

AC XY:

134340

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.997

AC:

1456599

AN:

1461706

Hom.:

726017

Cov.:

AF XY:

0.997

AC XY:

724902

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.879

Gnomad4 AMR exome

AF:

0.993

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.992

GnomAD4 genome

AF:

0.966

AC:

147115

AN:

152278

Hom.:

71268

Cov.:

AF XY:

0.967

AC XY:

72021

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.882

Gnomad4 AMR

AF:

0.986

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.978

Alfa

AF:

0.992

Hom.:

118193

Bravo

AF:

0.961

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.884

AC:

3339

ESP6500EA

AF:

1.00

AC:

8247

ExAC

AF:

0.989

AC:

119492

Asia WGS

AF:

0.991

AC:

3447

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

DNAH7-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

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

Benign

0.045

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.013

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.41

MetaRNN

Benign

6.8e-7

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-4.0

MutationTaster

Benign

0.0027

PrimateAI

Uncertain

0.51

PROVEAN

Benign

9.5

REVEL

Benign

0.25

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.068

MPC

0.039

ClinPred

0.020

GERP RS

5.1

Varity_R

0.093

gMVP

0.56

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

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