Variant 2-195884788-T-C 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.5560A>G(p.Ile1854Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,612,554 control chromosomes in the GnomAD database, including 1,608 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 460 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1148 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.58

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=0.0017811954).

BP6

Variant 2-195884788-T-C is Benign according to our data. Variant chr2-195884788-T-C is described in ClinVar as [Benign]. Clinvar id is 402750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-195884788-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 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.5560A>G	p.Ile1854Val	missense_variant	35/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.5560A>G	p.Ile1854Val	missense_variant	35/65	1	NM_018897.3	P1	Q8WXX0-1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9037

AN:

152158

Hom.:

457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0311

AC:

7750

AN:

248850

Hom.:

255

AF XY:

0.0295

AC XY:

3981

AN XY:

135048

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.0148

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0309

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0327

AC:

47710

AN:

1460278

Hom.:

1148

Cov.:

AF XY:

0.0318

AC XY:

23112

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0223

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.0323

Gnomad4 OTH exome

AF:

0.0352

GnomAD4 genome

AF:

0.0596

AC:

9069

AN:

152276

Hom.:

460

Cov.:

AF XY:

0.0568

AC XY:

4229

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0276

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.0249

Gnomad4 NFE

AF:

0.0309

Gnomad4 OTH

AF:

0.0540

Alfa

AF:

0.0347

Hom.:

227

Bravo

AF:

0.0634

TwinsUK

AF:

0.0340

AC:

126

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.130

AC:

480

ESP6500EA

AF:

0.0308

AC:

252

ExAC

AF:

0.0341

AC:

4118

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

EpiCase

AF:

0.0287

EpiControl

AF:

0.0301

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

Jan 06, 2020

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

0.083

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.011

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

MutationTaster

Benign

0.89

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.22

REVEL

Benign

0.062

Sift

Benign

0.80

Polyphen

0.0010

Vest4

0.063

MPC

0.028

ClinPred

0.015

GERP RS

5.7

Varity_R

0.089

gMVP

0.15

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