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rs730882228

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5

The NM_017785.5(SPDL1):​c.1724_1747del​(p.Ser575_Thr582del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000479 in 1,460,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SPDL1
NM_017785.5 inframe_deletion

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.40
Variant links:
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 5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Nonframeshift variant in NON repetitive region in NM_017785.5.
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-169604101-GAAAAGAAACTTCAAGCAAATTGGA-G is Pathogenic according to our data. Variant chr5-169604101-GAAAAGAAACTTCAAGCAAATTGGA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183325.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-169604101-GAAAAGAAACTTCAAGCAAATTGGA-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPDL1NM_017785.5 linkuse as main transcriptc.1724_1747del p.Ser575_Thr582del inframe_deletion 12/12 ENST00000265295.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPDL1ENST00000265295.9 linkuse as main transcriptc.1724_1747del p.Ser575_Thr582del inframe_deletion 12/121 NM_017785.5 P1Q96EA4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460780
Hom.:
0
AF XY:
0.00000413
AC XY:
3
AN XY:
726704
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neonatal death;CN228308:Severe primary microcephaly Pathogenic:1
Likely pathogenic, no assertion criteria providedresearchCenter for Genomic Medicine, King Faisal Specialist Hospital and Research CenterDec 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730882228; hg19: chr5-169031105; API