chr9-104101967-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006444.3(SMC2):c.644C>G(p.Ser215Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SMC2
NM_006444.3 missense
NM_006444.3 missense
Scores
7
11
1
Clinical Significance
Conservation
PhyloP100: 6.04
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.644C>G | p.Ser215Trp | missense_variant | 8/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.644C>G | p.Ser215Trp | missense_variant | 8/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.644C>G | p.Ser215Trp | missense_variant | 8/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.644C>G | p.Ser215Trp | missense_variant | 8/25 | 2 | P1 | ||
SMC2 | ENST00000440179.5 | c.209C>G | p.Ser70Trp | missense_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 26
GnomAD4 exome
Cov.:
26
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 | Feb 07, 2023 | The c.644C>G (p.S215W) alteration is located in exon 8 (coding exon 7) of the SMC2 gene. This alteration results from a C to G substitution at nucleotide position 644, causing the serine (S) at amino acid position 215 to be replaced by a tryptophan (W). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
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
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;D
Vest4
MutPred
Loss of disorder (P = 0.0019);.;Loss of disorder (P = 0.0019);Loss of disorder (P = 0.0019);
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
Publications
No publications associated with this variant yet.