17-42665545-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000251412.8(TUBG2):āc.676T>Cā(p.Ser226Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000798 in 1,614,024 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00048 ( 0 hom., cov: 32)
Exomes š: 0.00083 ( 3 hom. )
Consequence
TUBG2
ENST00000251412.8 missense
ENST00000251412.8 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 6.10
Genes affected
TUBG2 (HGNC:12419): (tubulin gamma 2) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic sister chromatid segregation. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17424786).
BS2
High Homozygotes in GnomAdExome4 at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBG2 | NM_016437.3 | c.676T>C | p.Ser226Pro | missense_variant | 7/11 | ENST00000251412.8 | NP_057521.1 | |
TUBG2 | NM_001320509.2 | c.703T>C | p.Ser235Pro | missense_variant | 8/12 | NP_001307438.1 | ||
TUBG2 | XM_047435757.1 | c.217T>C | p.Ser73Pro | missense_variant | 4/8 | XP_047291713.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBG2 | ENST00000251412.8 | c.676T>C | p.Ser226Pro | missense_variant | 7/11 | 1 | NM_016437.3 | ENSP00000251412.6 | ||
TUBG2 | ENST00000588870.1 | n.1074T>C | non_coding_transcript_exon_variant | 5/9 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000480 AC: 73AN: 152012Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000394 AC: 99AN: 251484Hom.: 0 AF XY: 0.000449 AC XY: 61AN XY: 135914
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GnomAD4 exome AF: 0.000831 AC: 1215AN: 1461894Hom.: 3 Cov.: 37 AF XY: 0.000814 AC XY: 592AN XY: 727248
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GnomAD4 genome AF: 0.000480 AC: 73AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74376
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.676T>C (p.S226P) alteration is located in exon 7 (coding exon 7) of the TUBG2 gene. This alteration results from a T to C substitution at nucleotide position 676, causing the serine (S) at amino acid position 226 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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