18-63901749-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P182Q) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 3160408.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	NM_002575.3	MANE Select	c.545C>T	p.Pro182Leu	missense	Exon 6 of 8	NP_002566.1	P05120
	SERPINB2	NM_001143818.2		c.545C>T	p.Pro182Leu	missense	Exon 7 of 9	NP_001137290.1	P05120

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000299502.9	TSL:1 MANE Select	c.545C>T	p.Pro182Leu	missense	Exon 6 of 8	ENSP00000299502.4	P05120
	ENSG00000289724	ENST00000418725.1	TSL:5	c.173C>T	p.Pro58Leu	missense	Exon 3 of 7	ENSP00000392381.1	H7C004
	SERPINB2	ENST00000457692.5	TSL:5	c.545C>T	p.Pro182Leu	missense	Exon 7 of 9	ENSP00000401645.1	P05120

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.4
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.39
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.94	P
Vest4		0.12
MutPred		0.48		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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