chr2-32357241-G-A

Position:

• chr2-32357241-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016252.4(BIRC6):​c.80G>A​(p.Arg27Gln) 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 NM_016252.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2815227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.80G>A	p.Arg27Gln	missense_variant	1/74	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.80G>A	p.Arg27Gln	missense_variant	1/74	1	NM_016252.4	ENSP00000393596	P2
BIRC6	ENST00000700518.1	c.80G>A	p.Arg27Gln	missense_variant	1/73			ENSP00000515025	A2
BIRC6	ENST00000700519.1	c.80G>A	p.Arg27Gln	missense_variant	1/74			ENSP00000515026

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1373114 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 677798

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.80G>A (p.R27Q) alteration is located in exon 1 (coding exon 1) of the BIRC6 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the arginine (R) at amino acid position 27 to be replaced by a glutamine (Q). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	0.75	N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.25
Sift	Benign	0.037	D
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.31		Loss of methylation at R27 (P = 0.0258);
MVP		0.49
MPC		1.5
ClinPred		0.72	D
GERP RS		3.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
gMVP		0.32

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

Other links and lift over

dbSNP: rs1420745785; hg19: chr2-32582309; COSMIC: COSV101428881;