2-32532171-G-GTGTGTGTGTGTGTGT

Variant names:

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

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+621insTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0039 (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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	NM_016252.4	MANE Select	c.12291+620_12291+621insTGTGTGTGTGTGTGT		intron	N/A	NP_057336.3
	MIR558	NR_030285.1		n.19_20insTGTGTGTGTGTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	NM_001378125.1		c.12288+620_12288+621insTGTGTGTGTGTGTGT		intron	N/A	NP_001365054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12291+620_12291+621insTGTGTGTGTGTGTGT		intron	N/A	ENSP00000393596.2
	MIR558	ENST00000384920.1	TSL:6	n.19_20insTGTGTGTGTGTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	ENST00000700518.1		c.12240+620_12240+621insTGTGTGTGTGTGTGT		intron	N/A	ENSP00000515025.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 163 AN: 149240 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00133

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.000992

Gnomad SAS AF: 0.000858

Gnomad FIN AF: 0.000787

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.000976

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00394 AC: 1479 AN: 375282 Hom.: 0 Cov.: 0 AF XY: 0.00387 AC XY: 827 AN XY: 213936

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

African (AFR) AF: 0.00390 AC: 40 AN: 10250

American (AMR) AF: 0.00407 AC: 145 AN: 35646

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 73 AN: 11518

East Asian (EAS) AF: 0.00192 AC: 25 AN: 13018

South Asian (SAS) AF: 0.00389 AC: 256 AN: 65882

European-Finnish (FIN) AF: 0.00851 AC: 268 AN: 31494

Middle Eastern (MID) AF: 0.00697 AC: 9 AN: 1292

European-Non Finnish (NFE) AF: 0.00323 AC: 614 AN: 189830

Other (OTH) AF: 0.00300 AC: 49 AN: 16352

⚠️ 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: 0.00109 AC: 163 AN: 149356 Hom.: 0 Cov.: 0 AF XY: 0.00110 AC XY: 80 AN XY: 72878

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

African (AFR) AF: 0.000591 AC: 24 AN: 40632

American (AMR) AF: 0.00133 AC: 20 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3438

East Asian (EAS) AF: 0.000995 AC: 5 AN: 5026

South Asian (SAS) AF: 0.000859 AC: 4 AN: 4658

European-Finnish (FIN) AF: 0.000787 AC: 8 AN: 10168

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.00141 AC: 95 AN: 67180

Other (OTH) AF: 0.000965 AC: 2 AN: 2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0126 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;