17-57584109-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138962.4. 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
	MSI2	NM_138962.4	MANE Select	c.455-12759T>C		intron	N/A	NP_620412.1	Q96DH6-1
	MSI2	NM_001322250.2		c.389-12759T>C		intron	N/A	NP_001309179.1	B4DHE8
	MSI2	NM_001322251.2		c.455-12759T>C		intron	N/A	NP_001309180.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI2	ENST00000284073.7	TSL:1 MANE Select	c.455-12759T>C		intron	N/A	ENSP00000284073.2	Q96DH6-1
	MSI2	ENST00000579180.2	TSL:1	c.143-12759T>C		intron	N/A	ENSP00000462264.1	Q96DH6-3
	MSI2	ENST00000902711.1		c.539-12759T>C		intron	N/A	ENSP00000572770.1

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

African (AFR) AF: 0.735 AC: 30427 AN: 41404

American (AMR) AF: 0.718 AC: 10967 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1946 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3543 AN: 5152

South Asian (SAS) AF: 0.612 AC: 2941 AN: 4806

European-Finnish (FIN) AF: 0.570 AC: 6012 AN: 10552

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.647 AC: 43953 AN: 67970

Other (OTH) AF: 0.626 AC: 1318 AN: 2106

Alfa AF: 0.651 Hom.: 126265

Bravo AF: 0.683

Asia WGS AF: 0.660 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.73
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs888115; hg19: chr17-55661470;