NM_170675.5:c.1418A>C

Variant names:

• chr15-36892189-T-G
• NM_170675.5:c.1418A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_170675.5(MEIS2):​c.1418A>C​(p.Asp473Ala) variant causes a missense change involving the alteration of a conserved nucleotide. 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: MEIS2 NM_170675.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.1418A>C	p.Asp473Ala	missense_variant	Exon 12 of 12	ENST00000561208.6	NP_733775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIS2	ENST00000561208.6	c.1418A>C	p.Asp473Ala	missense_variant	Exon 12 of 12	1	NM_170675.5	ENSP00000453793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies Uncertain:1

May 07, 2025

Institute of Immunology and Genetics Kaiserslautern

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG Criteria: PM2, PP3; Variant was found in heterozygous state; potentially de novo mother non-carrier, father not available -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		7.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N;N
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;D
Vest4		0.83
MutPred		0.62		Loss of sheet (P = 0.0104);.;
MVP		0.90
MPC		0.021
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.79
Mutation Taster		=75/25	polymorphism

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

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Other links and lift over

hg19: chr15-37184390;