chr6-38909714-T-C
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001206927.2(DNAH8):āc.9710T>Cā(p.Val3237Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00028 ( 0 hom., cov: 32)
Exomes š: 0.00029 ( 0 hom. )
Consequence
DNAH8
NM_001206927.2 missense
NM_001206927.2 missense
Scores
3
5
7
Clinical Significance
Conservation
PhyloP100: 7.64
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.16387165).
BP6
Variant 6-38909714-T-C is Benign according to our data. Variant chr6-38909714-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238658.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.9710T>C | p.Val3237Ala | missense_variant | 65/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.783-1877A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.9710T>C | p.Val3237Ala | missense_variant | 65/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.9059T>C | p.Val3020Ala | missense_variant | 63/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.9710T>C | p.Val3237Ala | missense_variant | 64/82 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000327 AC: 82AN: 251094Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135708
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GnomAD4 exome AF: 0.000289 AC: 422AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.000296 AC XY: 215AN XY: 727200
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GnomAD4 genome AF: 0.000283 AC: 43AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74366
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.9710T>C (p.V3237A) alteration is located in exon 65 (coding exon 64) of the DNAH8 gene. This alteration results from a T to C substitution at nucleotide position 9710, causing the valine (V) at amino acid position 3237 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Polyphen
0.99
.;.;D
Vest4
MVP
MPC
0.63
ClinPred
T
GERP RS
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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