2-32532171-G-GTGT

Variant names:

• chr2-32532171-G-GTGT
• rs35999329
• NM_016252.4:c.12291+620_12291+621insTGT

Variant summary

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

The NM_016252.4(BIRC6):​c.12291+620_12291+621insTGT 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 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 2 publications found

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insTGT		intron_variant	Intron 61 of 73	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12291+620_12291+621insTGT		intron_variant	Intron 61 of 73	1	NM_016252.4	ENSP00000393596.2

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149342 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000266 AC: 100 AN: 376368 Hom.: 0 Cov.: 0 AF XY: 0.000233 AC XY: 50 AN XY: 214526

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000586 AC: 6 AN: 10244

American (AMR) AF: 0.000560 AC: 20 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.000432 AC: 5 AN: 11568

East Asian (EAS) AF: 0.0000767 AC: 1 AN: 13040

South Asian (SAS) AF: 0.000197 AC: 13 AN: 66062

European-Finnish (FIN) AF: 0.0000629 AC: 2 AN: 31792

Middle Eastern (MID) AF: 0.000773 AC: 1 AN: 1294

European-Non Finnish (NFE) AF: 0.000242 AC: 46 AN: 190256

Other (OTH) AF: 0.000366 AC: 6 AN: 16382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149460 Hom.: 0 Cov.: 0 AF XY: 0.0000274 AC XY: 2 AN XY: 72930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000246 AC: 1 AN: 40646

American (AMR) AF: 0.00 AC: 0 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.00 AC: 0 AN: 4660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67228

Other (OTH) AF: 0.00 AC: 0 AN: 2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs35999329; hg19: chr2-32757238;