Variant 2-195738049-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018897.3(DNAH7):c.11947C>T(p.Arg3983Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00898 in 1,613,950 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 90 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 2.35

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014028847).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3 linkuse as main transcript	c.11947C>T	p.Arg3983Trp	missense_variant	65/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.11947C>T	p.Arg3983Trp	missense_variant	65/65	1	NM_018897.3	P1	Q8WXX0-1
DNAH7	ENST00000409063.5 linkuse as main transcript	c.1396C>T	p.Arg466Trp	missense_variant	10/10	1			Q8WXX0-2
DNAH7	ENST00000438565.1 linkuse as main transcript	c.*78C>T		3_prime_UTR_variant	3/3	3
DNAH7	ENST00000484183.1 linkuse as main transcript	n.445C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1090

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00830

AC:

2069

AN:

249300

Hom.:

AF XY:

0.00875

AC XY:

1184

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00758

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00917

AC:

13406

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6632

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.00436

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00767

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00780

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152276

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00908

Hom.:

Bravo

AF:

0.00632

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00181

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00866

AC:

1047

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	DNAH7: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Primary ciliary dyskinesia;C0037221:Abdominal situs inversus

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS)

Dec 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.75

LIST_S2

Pathogenic

1.0

D;D

MetaRNN

Benign

0.014

T;T

MetaSVM

Uncertain

-0.066

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-7.7

D;D

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

.;D

Vest4

0.95

MVP

0.48

MPC

0.24

ClinPred

0.12

GERP RS

3.6

Varity_R

0.86

gMVP

0.91

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