11-102350018-C-G

Variant names:

• chr11-102350018-C-G
• NM_001166.5:c.164C>G
• BIRC2 p.Thr55Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166.5(BIRC2):​c.164C>G​(p.Thr55Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T55P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BIRC2 NM_001166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 0 publications found

Genes affected

BIRC2 (HGNC:590): (baculoviral IAP repeat containing 2) The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12909225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166.5. 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
	BIRC2	NM_001166.5	MANE Select	c.164C>G	p.Thr55Ser	missense	Exon 2 of 9	NP_001157.1	Q13490-1
	BIRC2	NM_001256163.1		c.164C>G	p.Thr55Ser	missense	Exon 2 of 9	NP_001243092.1	Q13490-1
	BIRC2	NM_001256166.2		c.17C>G	p.Thr6Ser	missense	Exon 2 of 9	NP_001243095.1	Q13490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC2	ENST00000227758.7	TSL:1 MANE Select	c.164C>G	p.Thr55Ser	missense	Exon 2 of 9	ENSP00000227758.2	Q13490-1
	BIRC2	ENST00000613397.4	TSL:1	c.164C>G	p.Thr55Ser	missense	Exon 2 of 9	ENSP00000477613.1	Q13490-1
	BIRC2	ENST00000527910.5	TSL:1	n.1893C>G		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.67	N
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.065
Sift	Benign	0.52	T
Sift4G	Benign	0.61	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.27
Mutation Taster		=88/12	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-102220749;