chr9-104102066-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006444.3(SMC2):c.743G>A(p.Arg248His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,608,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006444.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.743G>A | p.Arg248His | missense_variant | 8/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.743G>A | p.Arg248His | missense_variant | 8/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.743G>A | p.Arg248His | missense_variant | 8/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.743G>A | p.Arg248His | missense_variant | 8/25 | 2 | P1 | ||
SMC2 | ENST00000440179.5 | c.308G>A | p.Arg103His | missense_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250668Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135660
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1456700Hom.: 0 Cov.: 30 AF XY: 0.0000221 AC XY: 16AN XY: 725044
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2023 | The c.743G>A (p.R248H) alteration is located in exon 8 (coding exon 7) of the SMC2 gene. This alteration results from a G to A substitution at nucleotide position 743, causing the arginine (R) at amino acid position 248 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at