17-57335100-A-G

Position:

• chr17-57335100-A-G

Variant summary

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

The NM_138962.4(MSI2):​c.313-66279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,158 control chromosomes in the GnomAD database, including 3,717 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 0.16 (3717 hom., cov: 32)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSI2	NM_138962.4	c.313-66279A>G		intron_variant		ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.313-66279A>G		intron_variant		1	NM_138962.4	ENSP00000284073	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23842 AN: 152042 Hom.: 3703 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.157 AC: 23904 AN: 152158 Hom.: 3717 Cov.: 32 AF XY: 0.157 AC XY: 11684 AN XY: 74406

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0491 Hom.: 614

Bravo AF: 0.179

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9890811; hg19: chr17-55412461;