rs1037863
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001370.2(DNAH6):c.786G>A(p.Leu262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 1,544,810 control chromosomes in the GnomAD database, including 689,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.92 ( 64732 hom., cov: 31)
Exomes 𝑓: 0.95 ( 624343 hom. )
Consequence
DNAH6
NM_001370.2 synonymous
NM_001370.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.61
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 2-84544356-G-A is Benign according to our data. Variant chr2-84544356-G-A is described in ClinVar as [Benign]. Clinvar id is 402732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.61 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH6 | NM_001370.2 | c.786G>A | p.Leu262= | synonymous_variant | 5/77 | ENST00000389394.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH6 | ENST00000389394.8 | c.786G>A | p.Leu262= | synonymous_variant | 5/77 | 5 | NM_001370.2 | P1 | |
DNAH6 | ENST00000494025.1 | n.230-3932G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
DNAH6 | ENST00000476689.5 | n.537-3932G>A | intron_variant, non_coding_transcript_variant | 2 | |||||
DNAH6 | ENST00000468661.1 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.921 AC: 140005AN: 151998Hom.: 64701 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
140005
AN:
151998
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.953 AC: 148898AN: 156226Hom.: 71046 AF XY: 0.955 AC XY: 79059AN XY: 82776
GnomAD3 exomes
AF:
AC:
148898
AN:
156226
Hom.:
AF XY:
AC XY:
79059
AN XY:
82776
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.947 AC: 1318246AN: 1392694Hom.: 624343 Cov.: 38 AF XY: 0.947 AC XY: 651145AN XY: 687366
GnomAD4 exome
AF:
AC:
1318246
AN:
1392694
Hom.:
Cov.:
38
AF XY:
AC XY:
651145
AN XY:
687366
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.921 AC: 140092AN: 152116Hom.: 64732 Cov.: 31 AF XY: 0.923 AC XY: 68617AN XY: 74360
GnomAD4 genome
?
AF:
AC:
140092
AN:
152116
Hom.:
Cov.:
31
AF XY:
AC XY:
68617
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3350
AN:
3468
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 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 - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at