18-63901749-C-T

Variant names:

• chr18-63901749-C-T
• rs2049992171
• NM_002575.3:c.545C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_002575.3(SERPINB2):​c.545C>T​(p.Pro182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43

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]

ENSG00000289724 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3050558).
• BP6: Variant 18-63901749-C-T is Benign according to our data. Variant chr18-63901749-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3160408.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.545C>T	p.Pro182Leu	missense_variant	Exon 6 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.545C>T	p.Pro182Leu	missense_variant	Exon 7 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.545C>T	p.Pro182Leu	missense_variant	Exon 6 of 8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.545C>T	p.Pro182Leu	missense_variant	Exon 6 of 8	1	NM_002575.3	ENSP00000299502.4
ENSG00000289724	ENST00000397996.6	c.173C>T	p.Pro58Leu	missense_variant	Exon 3 of 8	5		ENSP00000381082.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 26, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.38	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.23	.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.39
Sift	Benign	0.23	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.94	P;P
Vest4		0.12
MutPred		0.48		Loss of disorder (P = 0.0388);Loss of disorder (P = 0.0388);
MVP		0.49
MPC		0.038
ClinPred		0.88	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs2049992171; hg19: chr18-61568983; COSMIC: COSV104605677; COSMIC: COSV104605677;