chr2-66567466-C-T

Variant names:

• chr2-66567466-C-T
• NM_002398.3:c.979C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002398.3(MEIS1):​c.979C>T​(p.Arg327Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEIS1 NM_002398.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

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.979C>T	p.Arg327Trp	missense	Exon 10 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.979C>T	p.Arg327Trp	missense	Exon 10 of 13	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.979C>T	p.Arg327Trp	missense	Exon 10 of 11	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.973C>T	p.Arg325Trp	missense	Exon 9 of 11	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	4.7	H
PhyloP100		4.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.82		Gain of catalytic residue at W322 (P = 0.0351)
MVP		0.98
MPC		1.7
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.78
gMVP		1.0
Mutation Taster		=11/89	disease causing

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

Other links and lift over

hg19: chr2-66794598; COSMIC: COSV55490618;