chr17-57530230-T-C

Variant names:

• chr17-57530230-T-C
• rs1024820
• NM_138962.4:c.454+506T>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.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
• Publications: 5 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MSI2	NM_138962.4	c.454+506T>C		intron_variant	Intron 7 of 13	ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.454+506T>C		intron_variant	Intron 7 of 13	1	NM_138962.4	ENSP00000284073.2

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

African (AFR) AF: 0.823 AC: 34150 AN: 41480

American (AMR) AF: 0.614 AC: 9392 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3960 AN: 5172

South Asian (SAS) AF: 0.658 AC: 3162 AN: 4806

European-Finnish (FIN) AF: 0.788 AC: 8335 AN: 10576

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45649 AN: 67968

Other (OTH) AF: 0.685 AC: 1445 AN: 2110

Alfa AF: 0.682 Hom.: 49714

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
PhyloP100		-1.0
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: rs1024820; hg19: chr17-55607591;