chr2-32532171-G-GTGTGTGTGTGT

Variant names:

• chr2-32532135-GTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG-GTGTGTGTGTGT
• NM_016252.4:c.12291+598_12291+622delGTGTGTGTGTGTGTGTGTGTGTGGT

Variant summary

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

The NM_016252.4(BIRC6):​c.12291+598_12291+622delGTGTGTGTGTGTGTGTGTGTGTGGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 0 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	NM_016252.4	MANE Select	c.12291+598_12291+622delGTGTGTGTGTGTGTGTGTGTGTGGT		intron	N/A	NP_057336.3	Q9NR09
	BIRC6	NM_001378125.1		c.12288+598_12288+622delGTGTGTGTGTGTGTGTGTGTGTGGT		intron	N/A	NP_001365054.1
	MIR558	NR_030285.1		n.-4_21delGTGTGTGTGTGTGTGTGTGTGTGGT		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12291+596_12291+620delGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000393596.2	Q9NR09
	BIRC6	ENST00000700518.1		c.12240+596_12240+620delGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000515025.1	A0A8V8TQB4
	BIRC6	ENST00000700519.1		c.12231+596_12231+620delGTGTGTGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000515026.1	A0A8V8TR92

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-32757202;