dbSNP rs746862134: MINDY2:p.Pro202Leu (chr15-58772000-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040450.3(MINDY2):c.605C>T(p.Pro202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

1 publications found

Variant links:

Genes affected

MINDY2 (HGNC:26954): (MINDY lysine 48 deubiquitinase 2) Enables cysteine-type peptidase activity and polyubiquitin modification-dependent protein binding activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MINDY2 links:

MINDY2-DT (HGNC:55889): (MINDY2 divergent transcript)

MINDY2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23333108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040450.3. 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
	MINDY2	NM_001040450.3	MANE Select	c.605C>T	p.Pro202Leu	missense	Exon 1 of 9	NP_001035540.1	Q8NBR6-1
	MINDY2	NM_001040453.3		c.605C>T	p.Pro202Leu	missense	Exon 1 of 9	NP_001035543.1	Q8NBR6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MINDY2	ENST00000559228.6	TSL:2 MANE Select	c.605C>T	p.Pro202Leu	missense	Exon 1 of 9	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3	TSL:1	c.605C>T	p.Pro202Leu	missense	Exon 1 of 9	ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9	TSL:1	n.605C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000326194.5	J3KNL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000875

AC:

AN:

228484

AF XY:

0.00000811

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000995

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1439080

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32928

American (AMR)

AF:

0.00

AC:

AN:

41578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24020

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

81960

European-Finnish (FIN)

AF:

0.0000382

AC:

AN:

52334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000454

AC:

AN:

1101652

Other (OTH)

AF:

0.00

AC:

AN:

59412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.82

M_CAP

Benign

0.024

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.88

PhyloP100

1.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.1

REVEL

Benign

0.11

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.023

Polyphen

0.98

Vest4

0.25

MutPred

0.23

Loss of loop (P = 0.0153)

MVP

0.61

MPC

0.085

ClinPred

0.50

GERP RS

4.1

Varity_R

0.22

gMVP

0.29

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over