Variant 2-84544443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001370.2(DNAH6):c.873C>T(p.Ser291Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,528,912 control chromosomes in the GnomAD database, including 640,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 53456 hom., cov: 32)

Exomes 𝑓: 0.92 ( 587436 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.457

Variant links:

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 links:

DNAH6 (HGNC:):

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-84544443-C-T is Benign according to our data. Variant chr2-84544443-C-T is described in ClinVar as [Benign]. Clinvar id is 402733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.457 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.873C>T	p.Ser291Ser	synonymous_variant	5/77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.873C>T	p.Ser291Ser	synonymous_variant	5/77	5	NM_001370.2	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1 linkuse as main transcript	n.230-3845C>T		intron_variant		1
DNAH6	ENST00000476689.5 linkuse as main transcript	n.537-3845C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124372

AN:

151980

Hom.:

53448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.890

Gnomad FIN

AF:

0.955

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.847

GnomAD3 exomes

AF:

0.911

AC:

140725

AN:

154432

Hom.:

64835

AF XY:

0.914

AC XY:

74884

AN XY:

81936

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.937

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.889

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.932

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.921

AC:

1268318

AN:

1376814

Hom.:

587436

Cov.:

AF XY:

0.921

AC XY:

626734

AN XY:

680216

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.931

Gnomad4 ASJ exome

AF:

0.934

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.890

Gnomad4 FIN exome

AF:

0.957

Gnomad4 NFE exome

AF:

0.933

Gnomad4 OTH exome

AF:

0.900

GnomAD4 genome

AF:

0.818

AC:

124418

AN:

152098

Hom.:

53456

Cov.:

AF XY:

0.822

AC XY:

61129

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.526

Gnomad4 AMR

AF:

0.891

Gnomad4 ASJ

AF:

0.936

Gnomad4 EAS

AF:

0.986

Gnomad4 SAS

AF:

0.890

Gnomad4 FIN

AF:

0.955

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.848

Alfa

AF:

0.877

Hom.:

27044

Bravo

AF:

0.803

Asia WGS

AF:

0.908

AC:

3150

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 01, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 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

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.74

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