2-84670377-A-G
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_001370.2(DNAH6):āc.6356A>Gā(p.Tyr2119Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,543,308 control chromosomes in the GnomAD database, including 633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.022 ( 50 hom., cov: 33)
Exomes š: 0.024 ( 583 hom. )
Consequence
DNAH6
NM_001370.2 missense
NM_001370.2 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAH6. . Gene score misZ 3.5535 (greater than the threshold 3.09). Trascript score misZ 3.4022 (greater than threshold 3.09). GenCC has associacion of gene with male infertility with azoospermia or oligozoospermia due to single gene mutation.
BP4
Computational evidence support a benign effect (MetaRNN=0.0058374703).
BP6
Variant 2-84670377-A-G is Benign according to our data. Variant chr2-84670377-A-G is described in ClinVar as [Benign]. Clinvar id is 402739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH6 | NM_001370.2 | c.6356A>G | p.Tyr2119Cys | missense_variant | 39/77 | ENST00000389394.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH6 | ENST00000389394.8 | c.6356A>G | p.Tyr2119Cys | missense_variant | 39/77 | 5 | NM_001370.2 | P1 | |
DNAH6 | ENST00000602588.1 | n.584A>G | non_coding_transcript_exon_variant | 4/11 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0217 AC: 3303AN: 152212Hom.: 50 Cov.: 33
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GnomAD3 exomes AF: 0.0269 AC: 4126AN: 153544Hom.: 83 AF XY: 0.0294 AC XY: 2382AN XY: 81036
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GnomAD4 exome AF: 0.0244 AC: 33895AN: 1390978Hom.: 583 Cov.: 28 AF XY: 0.0260 AC XY: 17841AN XY: 686070
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GnomAD4 genome AF: 0.0217 AC: 3305AN: 152330Hom.: 50 Cov.: 33 AF XY: 0.0223 AC XY: 1660AN XY: 74488
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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 | Jan 09, 2019 | This variant is associated with the following publications: (PMID: 29767709) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
D;D
Polyphen
D;D
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at