chr2-66437931-C-A

Variant names:

• chr2-66437931-C-A
• rs558509818
• NM_002398.3:c.207C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002398.3(MEIS1):​c.207C>A​(p.Asp69Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEIS1 NM_002398.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002398.3. 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
	MEIS1	NM_002398.3	MANE Select	c.207C>A	p.Asp69Glu	missense	Exon 2 of 13	NP_002389.1	O00470-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	ENST00000272369.14	TSL:1 MANE Select	c.207C>A	p.Asp69Glu	missense	Exon 2 of 13	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.207C>A	p.Asp69Glu	missense	Exon 2 of 11	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.201C>A	p.Asp67Glu	missense	Exon 1 of 11	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440434 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 714324

African (AFR) AF: 0.00 AC: 0 AN: 32938

American (AMR) AF: 0.00 AC: 0 AN: 41238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 38594

South Asian (SAS) AF: 0.00 AC: 0 AN: 83012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101234

Other (OTH) AF: 0.00 AC: 0 AN: 59700

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.19
Sift	Benign	0.25	T
Sift4G	Benign	0.56	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.31		Gain of ubiquitination at K72 (P = 0.1679)
MVP		0.60
MPC		1.4
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.58
gMVP		0.66
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs558509818; hg19: chr2-66665063;