17-57462885-A-C

Variant names:

• chr17-57462885-A-C
• rs1822381
• NM_138962.4:c.405+61414A>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.405+61414A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,150 control chromosomes in the GnomAD database, including 18,198 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 0.44 (18198 hom., cov: 33)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSI2	NM_138962.4	c.405+61414A>C		intron_variant	Intron 6 of 13	ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.405+61414A>C		intron_variant	Intron 6 of 13	1	NM_138962.4	ENSP00000284073.2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67532 AN: 152034 Hom.: 18189 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.444 AC: 67562 AN: 152150 Hom.: 18198 Cov.: 33 AF XY: 0.448 AC XY: 33337 AN XY: 74394

African (AFR) AF: 0.129 AC: 5372 AN: 41528

American (AMR) AF: 0.576 AC: 8805 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2976 AN: 5182

South Asian (SAS) AF: 0.718 AC: 3460 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4684 AN: 10586

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38302 AN: 67970

Other (OTH) AF: 0.503 AC: 1061 AN: 2110

Alfa AF: 0.520 Hom.: 16027

Bravo AF: 0.438

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		0.33
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: rs1822381; hg19: chr17-55540246;