18-63901869-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002575.3(SERPINB2):​c.665T>G​(p.Phe222Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SERPINB2
NM_002575.3 missense

Scores

13
4
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.13
Variant links:
Genes affected
SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINB2NM_002575.3 linkc.665T>G p.Phe222Cys missense_variant Exon 6 of 8 ENST00000299502.9 NP_002566.1 P05120
SERPINB2NM_001143818.2 linkc.665T>G p.Phe222Cys missense_variant Exon 7 of 9 NP_001137290.1 P05120
SERPINB2XM_024451192.2 linkc.665T>G p.Phe222Cys missense_variant Exon 6 of 8 XP_024306960.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINB2ENST00000299502.9 linkc.665T>G p.Phe222Cys missense_variant Exon 6 of 8 1 NM_002575.3 ENSP00000299502.4 P05120
ENSG00000289724ENST00000397996.6 linkc.293T>G p.Phe98Cys missense_variant Exon 3 of 8 5 ENSP00000381082.2 H7BYS2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.74
D;D
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.76
.;T
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.78
D
MutationAssessor
Pathogenic
4.9
H;H
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-7.7
D;D
REVEL
Pathogenic
0.97
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.98
MutPred
0.94
Gain of catalytic residue at P221 (P = 0.0135);Gain of catalytic residue at P221 (P = 0.0135);
MVP
0.86
MPC
0.13
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.98
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776993429; hg19: chr18-61569103; API