17-57445494-T-C

Position:

• chr17-57445494-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.405+44023T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,454 control chromosomes in the GnomAD database, including 22,906 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 0.53 (22906 hom., cov: 29)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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]

MSI2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSI2	NM_138962.4	c.405+44023T>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.405+44023T>C		intron_variant		1	NM_138962.4	ENSP00000284073.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80360 AN: 151336 Hom.: 22901 Cov.: 29

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.531 AC: 80389 AN: 151454 Hom.: 22906 Cov.: 29 AF XY: 0.532 AC XY: 39325 AN XY: 73978

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.582

Alfa AF: 0.601 Hom.: 35658

Bravo AF: 0.528

Asia WGS AF: 0.711 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.68

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: rs11657292; hg19: chr17-55522855;