chr9-104102017-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_006444.3(SMC2):c.694C>T(p.Arg232Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,458,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
SMC2
NM_006444.3 missense
NM_006444.3 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 4.77
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 Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.836
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.694C>T | p.Arg232Cys | missense_variant | 8/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.694C>T | p.Arg232Cys | missense_variant | 8/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.694C>T | p.Arg232Cys | missense_variant | 8/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.694C>T | p.Arg232Cys | missense_variant | 8/25 | 2 | P1 | ||
SMC2 | ENST00000440179.5 | c.259C>T | p.Arg87Cys | missense_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1458850Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 725620
GnomAD4 exome
AF:
AC:
10
AN:
1458850
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
725620
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
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 06, 2023 | The c.694C>T (p.R232C) alteration is located in exon 8 (coding exon 7) of the SMC2 gene. This alteration results from a C to T substitution at nucleotide position 694, causing the arginine (R) at amino acid position 232 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;T;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MutPred
Gain of catalytic residue at L233 (P = 0.0112);.;Gain of catalytic residue at L233 (P = 0.0112);Gain of catalytic residue at L233 (P = 0.0112);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at