rs1822381

chr17-57462885-A-Cchr17-57462885-A-Gchr17-57462885-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	UniProt
MSI2	NM_138962.4	c.405+61414A>C		intron_variant		ENST00000284073.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSI2	ENST00000284073.7	c.405+61414A>C		intron_variant		1	NM_138962.4	P1

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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.503

Alfa AF: 0.517 Hom.: 11196

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

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: rs1822381; hg19: chr17-55540246;