chr2-32532171-G-GTGTGTGTGTGT

Position:

• chr2-32532171-G-GTGTGTGTGTGT

Variant summary

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

The ENST00000421745.7(BIRC6):​c.12291+620_12291+621insTGTGTGTGTGT 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 0.00058 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 ENST00000421745.7 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 87 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insTGTGTGTGTGT		intron_variant		ENST00000421745.7	NP_057336.3
MIR558	NR_030285.1	n.19_20insTGTGTGTGTGT		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+621insTGTGTGTGTGT		intron_variant		1	NM_016252.4	ENSP00000393596	P2
MIR558	ENST00000384920.1	n.19_20insTGTGTGTGTGT		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.000569 AC: 85 AN: 149286 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000617

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.000600

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000793

Gnomad SAS AF: 0.000643

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000625

Gnomad OTH AF: 0.000487

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00764 AC: 2868 AN: 375564 Hom.: 0 Cov.: 0 AF XY: 0.00776 AC XY: 1661 AN XY: 214070

Gnomad4 AFR exome AF: 0.00899

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00307

Gnomad4 SAS exome AF: 0.00850

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.00627

Gnomad4 OTH exome AF: 0.00587

GnomAD4 genome AF: 0.000582 AC: 87 AN: 149402 Hom.: 0 Cov.: 0 AF XY: 0.000672 AC XY: 49 AN XY: 72900

Gnomad4 AFR AF: 0.000640

Gnomad4 AMR AF: 0.000666

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000795

Gnomad4 SAS AF: 0.000644

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000625

Gnomad4 OTH AF: 0.000482

Alfa AF: 0.0158 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;