rs144548752

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_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. 15/22 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Illumina, Ambry Genetics
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P

MEIS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

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 VariationId is 2645154.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 122 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170675.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEIS2	NM_170675.5	MANE Select	c.1262A>G	p.His421Arg	missense	Exon 12 of 12	NP_733775.1	O14770-1
MEIS2	NM_001220482.2		c.1241A>G	p.His414Arg	missense	Exon 13 of 13	NP_001207411.1	O14770-4
MEIS2	NM_170676.5		c.1241A>G	p.His414Arg	missense	Exon 12 of 12	NP_733776.1	O14770-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEIS2	ENST00000561208.6	TSL:1 MANE Select	c.1262A>G	p.His421Arg	missense	Exon 12 of 12	ENSP00000453793.1	O14770-1
MEIS2	ENST00000338564.9	TSL:1	c.1241A>G	p.His414Arg	missense	Exon 13 of 13	ENSP00000341400.4	O14770-4
MEIS2	ENST00000424352.6	TSL:1	c.*152A>G		3_prime_UTR	Exon 13 of 13	ENSP00000404185.2	O14770-2

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

GnomAD2 exomes

AF:

0.000805

AC:

202

AN:

250970

AF XY:

0.000833

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 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

African (AFR)

AF:

0.000299

AC:

AN:

33476

American (AMR)

AF:

0.000201

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.000655

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00157

AC:

1743

AN:

1111960

Other (OTH)

AF:

0.000729

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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

AF:

0.000803

AC:

122

AN:

152014

Hom.:

Cov.:

AF XY:

0.000741

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.000266

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

67998

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00126

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MEIS2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.12

Eigen

Benign

-0.035

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Benign

0.035

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

2.0

PhyloP100

4.7

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.2

REVEL

Benign

0.27

Sift

Uncertain

0.0050

Sift4G

Benign

0.26

Polyphen

0.0040

Vest4

0.33

MVP

0.83

MPC

0.0070

ClinPred

0.022

GERP RS

4.2

Varity_R

0.17

gMVP

0.58

Mutation Taster

=26/74

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over