17-57675040-G-C

Variant names:

• chr17-57675040-G-C
• rs1221930442
• NM_138962.4:c.859G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138962.4(MSI2):​c.859G>C​(p.Gly287Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G287S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MSI2 NM_138962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI2	NM_138962.4	MANE Select	c.859G>C	p.Gly287Arg	missense	Exon 12 of 14	NP_620412.1	Q96DH6-1
	MSI2	NM_001322250.2		c.847G>C	p.Gly283Arg	missense	Exon 12 of 14	NP_001309179.1	B4DHE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI2	ENST00000284073.7	TSL:1 MANE Select	c.859G>C	p.Gly287Arg	missense	Exon 12 of 14	ENSP00000284073.2	Q96DH6-1
	MSI2	ENST00000902711.1		c.943G>C	p.Gly315Arg	missense	Exon 13 of 15	ENSP00000572770.1
	MSI2	ENST00000902712.1		c.901G>C	p.Gly301Arg	missense	Exon 12 of 14	ENSP00000572771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.74	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.97	L
PhyloP100		9.6
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.83
MutPred		0.19		Gain of phosphorylation at S290 (P = 0.0847)
MVP		0.93
MPC		1.8
ClinPred		0.98	D
GERP RS		4.4
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.96

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: rs1221930442; hg19: chr17-55752401;