rs1024820

Positions:

• chr17-57530230-T-C

Variant summary

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

The NM_138962.4(MSI2):​c.454+506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,072 control chromosomes in the GnomAD database, including 39,756 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 0.72 (39756 hom., cov: 31)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSI2	NM_138962.4	c.454+506T>C		intron_variant		ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.454+506T>C		intron_variant		1	NM_138962.4	ENSP00000284073	P1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109188 AN: 151954 Hom.: 39705 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.719 AC: 109300 AN: 152072 Hom.: 39756 Cov.: 31 AF XY: 0.721 AC XY: 53612 AN XY: 74318

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.685

Alfa AF: 0.676 Hom.: 34409

Bravo AF: 0.716

Asia WGS AF: 0.674 AC: 2345 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	0.64
DANN	Benign	0.55

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: rs1024820; hg19: chr17-55607591;