19-5587702-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_014649.3(SAFB2):c.2704G>T(p.Gly902Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000715 in 1,398,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SAFB2
NM_014649.3 missense, splice_region
NM_014649.3 missense, splice_region
Scores
2
12
5
Splicing: ADA: 0.1239
2
Clinical Significance
Conservation
PhyloP100: 4.93
Publications
1 publications found
Genes affected
SAFB2 (HGNC:21605): (scaffold attachment factor B2) The protein encoded by this gene, along with its paralog (scaffold attachment factor B1), is a repressor of estrogen receptor alpha. The encoded protein binds scaffold/matrix attachment region (S/MAR) DNA and is involved in cell cycle regulation, apoptosis, differentiation, the stress response, and regulation of immune genes. [provided by RefSeq, May 2016]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152250
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000129 AC: 2AN: 155286 AF XY: 0.0000122 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
155286
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1398260Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1AN XY: 689652 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1398260
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
689652
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31524
American (AMR)
AF:
AC:
0
AN:
35510
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25106
East Asian (EAS)
AF:
AC:
1
AN:
35726
South Asian (SAS)
AF:
AC:
0
AN:
79080
European-Finnish (FIN)
AF:
AC:
0
AN:
49050
Middle Eastern (MID)
AF:
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1078632
Other (OTH)
AF:
AC:
0
AN:
57942
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.725
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000656 AC: 1AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74518 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
152368
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74518
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41600
American (AMR)
AF:
AC:
0
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
1
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68028
Other (OTH)
AF:
AC:
0
AN:
2114
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
May 10, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.2704G>T (p.G902W) alteration is located in exon 20 (coding exon 20) of the SAFB2 gene. This alteration results from a G to T substitution at nucleotide position 2704, causing the glycine (G) at amino acid position 902 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
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R903 (P = 0.0232);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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