rs77530912
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001003800.2(BICD2):c.1044G>A(p.Leu348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,610,772 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00051 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00096 ( 51 hom. )
Consequence
BICD2
NM_001003800.2 synonymous
NM_001003800.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.92
Genes affected
BICD2 (HGNC:17208): (BICD cargo adaptor 2) This gene is one of two human homologs of Drosophila bicaudal-D and a member of the Bicoid family. It has been implicated in dynein-mediated, minus end-directed motility along microtubules. It has also been reported to be a phosphorylation target of NIMA related kinase 8. Two alternative splice variants have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 9-92720318-C-T is Benign according to our data. Variant chr9-92720318-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 390790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.92 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000512 (78/152348) while in subpopulation EAS AF= 0.0149 (77/5184). AF 95% confidence interval is 0.0122. There are 2 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 78 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.1044G>A | p.Leu348= | synonymous_variant | 4/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.1044G>A | p.Leu348= | synonymous_variant | 4/8 | ||
BICD2 | XM_017014551.2 | c.1125G>A | p.Leu375= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.1044G>A | p.Leu348= | synonymous_variant | 4/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.1044G>A | p.Leu348= | synonymous_variant | 4/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000512 AC: 78AN: 152230Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000190 AC: 47AN: 247436Hom.: 1 AF XY: 0.000187 AC XY: 25AN XY: 133928
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GnomAD4 exome AF: 0.000959 AC: 1399AN: 1458424Hom.: 51 Cov.: 32 AF XY: 0.000932 AC XY: 676AN XY: 725018
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GnomAD4 genome ? AF: 0.000512 AC: 78AN: 152348Hom.: 2 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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