2-84529055-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_001370.2(DNAH6):c.551G>C(p.Arg184Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000654 in 1,550,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

DNAH6
NM_001370.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.255

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, DNAH6

BP4

Computational evidence support a benign effect (MetaRNN=0.02787289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.551G>C	p.Arg184Pro	missense_variant	4/77	ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.551G>C	p.Arg184Pro	missense_variant	4/77	5	NM_001370.2	P1	Q9C0G6-1
DNAH6	ENST00000494025.1 linkuse as main transcript	n.229+11004G>C		intron_variant, non_coding_transcript_variant		1
DNAH6	ENST00000468661.1 linkuse as main transcript	n.454+3317G>C		intron_variant, non_coding_transcript_variant		4
DNAH6	ENST00000476689.5 linkuse as main transcript	n.536+3317G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000323

AC:

AN:

151662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000369

AC:

AN:

157310

Hom.:

AF XY:

0.000409

AC XY:

AN XY:

83134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000868

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000690

AC:

966

AN:

1399202

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

479

AN XY:

690110

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000867

Gnomad4 OTH exome

AF:

0.000345

GnomAD4 genome

AF:

0.000323

AC:

AN:

151662

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.0000969

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000402

Hom.:

Bravo

AF:

0.000332

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000242

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.551G>C (p.R184P) alteration is located in exon 4 (coding exon 3) of the DNAH6 gene. This alteration results from a G to C substitution at nucleotide position 551, causing the arginine (R) at amino acid position 184 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.49

Cadd

Benign

5.1

Dann

Benign

0.82

DEOGEN2

Benign

0.0087

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.61

T;.

M_CAP

Benign

0.0059

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.11

Sift

Benign

0.30

T;T

Polyphen

0.0

B;B

Vest4

0.39

MVP

0.10

MPC

0.12

ClinPred

0.021

GERP RS

2.1

Varity_R

0.13

gMVP

0.59

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