Variant 11-102350233-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166.5(BIRC2):c.379A>T(p.Asn127Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BIRC2
NM_001166.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.292

Variant links:

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]

BIRC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101489395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BIRC2	NM_001166.5 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	2/9	ENST00000227758.7	NP_001157.1
BIRC2	NM_001256163.1 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	2/9		NP_001243092.1
BIRC2	NM_001256166.2 linkuse as main transcript	c.232A>T	p.Asn78Tyr	missense_variant	2/9		NP_001243095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC2	ENST00000227758.7 linkuse as main transcript	c.379A>T	p.Asn127Tyr	missense_variant	2/9	1	NM_001166.5	ENSP00000227758		Q13490-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.379A>T (p.N127Y) alteration is located in exon 2 (coding exon 1) of the BIRC2 gene. This alteration results from a A to T substitution at nucleotide position 379, causing the asparagine (N) at amino acid position 127 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.084

.;T;T;T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.062

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.64

T;.;T;T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;.;.;N

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.82

N;N;N;N;.;.

REVEL

Benign

0.044

Sift

Benign

0.45

T;T;T;T;.;.

Sift4G

Benign

0.38

T;T;T;T;T;T

Polyphen

0.26

.;B;.;.;.;B

Vest4

0.36

MutPred

0.20

.;Gain of phosphorylation at N127 (P = 0.0398);.;.;Gain of phosphorylation at N127 (P = 0.0398);Gain of phosphorylation at N127 (P = 0.0398);

MVP

0.70

MPC

0.067

ClinPred

0.44

GERP RS

4.3

Varity_R

0.086

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over