2-32532171-G-GTGTGTGTGT

Position:

• chr2-32532171-G-GTGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016252.4(BIRC6):​c.12291+620_12291+621insTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

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]

MIR558 (HGNC:32814): (microRNA 558) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insTGTGTGTGT		intron_variant		ENST00000421745.7	NP_057336.3
MIR558	NR_030285.1	n.19_20insTGTGTGTGT		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12291+620_12291+621insTGTGTGTGT		intron_variant		1	NM_016252.4	ENSP00000393596	P2
MIR558	ENST00000384920.1	n.19_20insTGTGTGTGT		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.000208 AC: 31 AN: 149332 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000667

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000387

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00466 AC: 1754 AN: 376162 Hom.: 0 Cov.: 0 AF XY: 0.00465 AC XY: 998 AN XY: 214404

Gnomad4 AFR exome AF: 0.00597

Gnomad4 AMR exome AF: 0.00848

Gnomad4 ASJ exome AF: 0.00797

Gnomad4 EAS exome AF: 0.00230

Gnomad4 SAS exome AF: 0.00545

Gnomad4 FIN exome AF: 0.00356

Gnomad4 NFE exome AF: 0.00378

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.000207 AC: 31 AN: 149450 Hom.: 0 Cov.: 0 AF XY: 0.000343 AC XY: 25 AN XY: 72924

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.0000666

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000429

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000387

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00706 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35999329; hg19: chr2-32757238;