Variant 15-36892345-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_170675.5(MEIS2):c.1262A>G(p.His421Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00122 in 1,613,800 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

MEIS2
NM_170675.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.69

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

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=0.03484735).

BP6

Variant 15-36892345-T-C is Benign according to our data. Variant chr15-36892345-T-C is described in ClinVar as [Benign]. Clinvar id is 2645154.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS2	NM_170675.5 linkuse as main transcript	c.1262A>G	p.His421Arg	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.1262A>G	p.His421Arg	missense_variant	12/12	1	NM_170675.5	ENSP00000453793		O14770-1

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000805

AC:

202

AN:

250970

Hom.:

AF XY:

0.000833

AC XY:

113

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00126

AC:

1844

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

915

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00157

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000803

AC:

122

AN:

152014

Hom.:

Cov.:

AF XY:

0.000741

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.000831

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000857

AC:

104

EpiCase

AF:

0.00142

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MEIS2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

MEIS2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.035

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.035

T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.26

T;T

Polyphen

0.0040

B;B

Vest4

0.33

MVP

0.83

MPC

0.0070

ClinPred

0.022

GERP RS

4.2

Varity_R

0.17

gMVP

0.58

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