17-57584109-T-C

Variant names:

• chr17-57584109-T-C
• rs888115
• NM_138962.4:c.455-12759T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138962.4(MSI2):​c.455-12759T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,930 control chromosomes in the GnomAD database, including 34,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34282 hom., cov: 30)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73

Genes affected

MSI2 (HGNC:18585): (musashi RNA binding protein 2) This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSI2	NM_138962.4	c.455-12759T>C		intron_variant	Intron 7 of 13	ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.455-12759T>C		intron_variant	Intron 7 of 13	1	NM_138962.4	ENSP00000284073.2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101637 AN: 151812 Hom.: 34234 Cov.: 30

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.670 AC: 101742 AN: 151930 Hom.: 34282 Cov.: 30 AF XY: 0.666 AC XY: 49441 AN XY: 74240

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.626

Alfa AF: 0.645 Hom.: 60596

Bravo AF: 0.683

Asia WGS AF: 0.660 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs888115; hg19: chr17-55661470;