chr9-104111713-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006444.3(SMC2):c.1153G>T(p.Ala385Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
SMC2
NM_006444.3 missense
NM_006444.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.44
Genes affected
SMC2 (HGNC:14011): (structural maintenance of chromosomes 2) Predicted to enable ATP binding activity; chromatin binding activity; and single-stranded DNA binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytoplasm; and nuclear lumen. Part of condensin complex. [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=0.24788764).
BS2
?
High AC in GnomAd at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.1153G>T | p.Ala385Ser | missense_variant | 10/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.1153G>T | p.Ala385Ser | missense_variant | 10/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.1153G>T | p.Ala385Ser | missense_variant | 10/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.1153G>T | p.Ala385Ser | missense_variant | 10/25 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152186Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250882Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135574
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461748Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727176
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74340
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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 | Apr 25, 2022 | The c.1153G>T (p.A385S) alteration is located in exon 10 (coding exon 9) of the SMC2 gene. This alteration results from a G to T substitution at nucleotide position 1153, causing the alanine (A) at amino acid position 385 to be replaced by a serine (S). 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
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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