Variant 2-66442986-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_002398.3(MEIS1):c.568A>G(p.Arg190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,454,448 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: 0.0000089 ( 0 hom. )

Consequence

MEIS1
NM_002398.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

MEIS1 (HGNC:7000): (Meis homeobox 1) Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. [provided by RefSeq, Jul 2008]

MEIS1 links:

MEIS1-AS2 (HGNC:40370): (MEIS1 antisense RNA 2)

MEIS1-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, MEIS1

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS1	NM_002398.3 linkuse as main transcript	c.568A>G	p.Arg190Gly	missense_variant	6/13	ENST00000272369.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS1	ENST00000272369.14 linkuse as main transcript	c.568A>G	p.Arg190Gly	missense_variant	6/13	1	NM_002398.3	P2	O00470-1
MEIS1-AS2	ENST00000666153.1 linkuse as main transcript	n.1236T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000827

AC:

AN:

241780

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131304

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1454448

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

723168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000992

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.568A>G (p.R190G) alteration is located in exon 6 (coding exon 6) of the MEIS1 gene. This alteration results from a A to G substitution at nucleotide position 568, causing the arginine (R) at amino acid position 190 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Benign

-0.72

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.4

D;D;.;D;D

Sift

Uncertain

0.023

D;D;.;D;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.99, 1.0, 0.72

.;D;.;D;P

Vest4

0.78

MutPred

0.27

Loss of glycosylation at S194 (P = 0.1131);Loss of glycosylation at S194 (P = 0.1131);Loss of glycosylation at S194 (P = 0.1131);.;.;

MVP

0.74

MPC

1.5

ClinPred

0.59

GERP RS

6.0

Varity_R

0.74

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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