chr9-104111759-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_006444.3(SMC2):c.1199G>T(p.Gly400Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,904 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
SMC2
NM_006444.3 missense
NM_006444.3 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 3.59
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 -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33364812).
BS2
?
High AC in GnomAdExome at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.1199G>T | p.Gly400Val | missense_variant | 10/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.1199G>T | p.Gly400Val | missense_variant | 10/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.1199G>T | p.Gly400Val | missense_variant | 10/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.1199G>T | p.Gly400Val | missense_variant | 10/25 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250900Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135600
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GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727142
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74354
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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 | Aug 02, 2021 | The c.1199G>T (p.G400V) 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 1199, causing the glycine (G) at amino acid position 400 to be replaced by a valine (V). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
D;D;D
Sift4G
Uncertain
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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