rs771001231
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP6_Very_StrongBS1BS2
The NM_001003800.2(BICD2):c.1741C>T(p.Arg581Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,598,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R581H) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
BICD2
NM_001003800.2 missense
NM_001003800.2 missense
Scores
11
7
Clinical Significance
Conservation
PhyloP100: 4.09
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 -15 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, BICD2
BP6
?
Variant 9-92718904-G-A is Benign according to our data. Variant chr9-92718904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000608 (88/1446628) while in subpopulation EAS AF= 0.000229 (9/39340). AF 95% confidence interval is 0.000119. There are 0 homozygotes in gnomad4_exome. There are 34 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.1741C>T | p.Arg581Cys | missense_variant | 5/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.1741C>T | p.Arg581Cys | missense_variant | 5/8 | ||
BICD2 | XM_017014551.2 | c.1822C>T | p.Arg608Cys | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.1741C>T | p.Arg581Cys | missense_variant | 5/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.1741C>T | p.Arg581Cys | missense_variant | 5/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000413 AC: 9AN: 218146Hom.: 0 AF XY: 0.0000251 AC XY: 3AN XY: 119692
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GnomAD4 exome AF: 0.0000608 AC: 88AN: 1446628Hom.: 0 Cov.: 32 AF XY: 0.0000473 AC XY: 34AN XY: 718604
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74332
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2021 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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