17-57675040-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_138962.4(MSI2):​c.859G>A​(p.Gly287Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MSI2 NM_138962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

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>A	p.Gly287Ser	missense	Exon 12 of 14	NP_620412.1	Q96DH6-1
	MSI2	NM_001322250.2		c.847G>A	p.Gly283Ser	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>A	p.Gly287Ser	missense	Exon 12 of 14	ENSP00000284073.2	Q96DH6-1
	MSI2	ENST00000902711.1		c.943G>A	p.Gly315Ser	missense	Exon 13 of 15	ENSP00000572770.1
	MSI2	ENST00000902712.1		c.901G>A	p.Gly301Ser	missense	Exon 12 of 14	ENSP00000572771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250288 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461720 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727154

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 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: 0.00000270 AC: 3 AN: 1111988

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	0.42	N
PhyloP100		9.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.47
Sift	Benign	0.43	T
Sift4G	Benign	0.18	T
Polyphen		0.96	P
Vest4		0.75
MutPred		0.14		Gain of glycosylation at G287 (P = 0.0085)
MVP		0.78
MPC		0.86
ClinPred		0.59	D
GERP RS		4.4
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.89
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;