chr5-169596559-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PVS1_ModeratePM2BP6_Moderate
The NM_017785.5(SPDL1):c.892-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,605,288 control chromosomes in the GnomAD database, including 1 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 1 hom. )
Consequence
SPDL1
NM_017785.5 splice_acceptor
NM_017785.5 splice_acceptor
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 8.15
Genes affected
SPDL1 (HGNC:26010): (spindle apparatus coiled-coil protein 1) This gene encodes a coiled-coil domain-containing protein that functions in mitotic spindle formation and chromosome segregation. The encoded protein plays a role in coordinating microtubule attachment by promoting recruitment of dynein proteins, and in mitotic checkpoint signaling. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.0770077 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.7, offset of -23, new splice context is: ctctcacttaattttattAGagg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 5-169596559-A-G is Benign according to our data. Variant chr5-169596559-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 753082.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPDL1 | NM_017785.5 | c.892-2A>G | splice_acceptor_variant | ENST00000265295.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPDL1 | ENST00000265295.9 | c.892-2A>G | splice_acceptor_variant | 1 | NM_017785.5 | P1 | |||
SPDL1 | ENST00000507232.5 | c.*672-2A>G | splice_acceptor_variant, NMD_transcript_variant | 1 | |||||
SPDL1 | ENST00000505977.1 | c.677-26A>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000401 AC: 61AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000469 AC: 114AN: 243154Hom.: 0 AF XY: 0.000501 AC XY: 66AN XY: 131690
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GnomAD4 exome AF: 0.000526 AC: 764AN: 1453002Hom.: 1 Cov.: 30 AF XY: 0.000573 AC XY: 414AN XY: 722758
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D
GERP RS
La Branchor
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 26
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at