chr1-224967581-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001367479.1(DNAH14):c.649A>G(p.Lys217Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DNAH14
NM_001367479.1 missense, splice_region
NM_001367479.1 missense, splice_region
Scores
4
8
6
Splicing: ADA: 0.1258
2
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH14 | NM_001367479.1 | c.649A>G | p.Lys217Glu | missense_variant, splice_region_variant | 6/86 | ENST00000682510.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH14 | ENST00000682510.1 | c.649A>G | p.Lys217Glu | missense_variant, splice_region_variant | 6/86 | NM_001367479.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1448922Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 720340
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1448922
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
720340
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Dec 22, 2023 | The c.649A>G (p.K217E) alteration is located in exon 6 (coding exon 5) of the DNAH14 gene. This alteration results from a A to G substitution at nucleotide position 649, causing the lysine (K) at amino acid position 217 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;.;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Pathogenic
D;T;D;D;D;T
Sift4G
Uncertain
T;T;T;D;T;T
Polyphen
1.0
.;D;D;D;D;D
Vest4
MutPred
0.57
.;Loss of methylation at K217 (P = 0.009);Loss of methylation at K217 (P = 0.009);Loss of methylation at K217 (P = 0.009);Loss of methylation at K217 (P = 0.009);Loss of methylation at K217 (P = 0.009);
MVP
MPC
0.39
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at