Variant 15-36892381-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_170675.5(MEIS2):c.1226C>T(p.Pro409Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MEIS2
NM_170675.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

MEIS2 (HGNC:7001): (Meis homeobox 2) This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. TALE homeobox proteins are highly conserved transcription regulators, and several members have been shown to be essential contributors to developmental programs. Multiple transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

MEIS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MEIS2. . Gene score misZ 2.4571 (greater than the threshold 3.09). Trascript score misZ 3.4197 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies.

BP4

Computational evidence support a benign effect (MetaRNN=0.17547902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS2	NM_170675.5 linkuse as main transcript	c.1226C>T	p.Pro409Leu	missense_variant	12/12	ENST00000561208.6	NP_733775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIS2	ENST00000561208.6 linkuse as main transcript	c.1226C>T	p.Pro409Leu	missense_variant	12/12	1	NM_170675.5	ENSP00000453793		O14770-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEIS2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 09, 2024

The MEIS2 c.1226C>T variant is predicted to result in the amino acid substitution p.Pro409Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.023

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.069

T;D

Polyphen

0.054

B;B

Vest4

0.26

MutPred

0.25

Loss of glycosylation at P409 (P = 0.0148);.;

MVP

0.49

MPC

0.0076

ClinPred

0.64

GERP RS

3.9

Varity_R

0.11

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over