rs201588285

Variant names:

• chr15-36892283-C-G
• rs201588285
• NM_170675.5:c.1324G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-36892283-C-G
• chr15-36892283-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_170675.5(MEIS2):​c.1324G>C​(p.Gly442Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MEIS2 NM_170675.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29200846).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	NM_170675.5	MANE Select	c.1324G>C	p.Gly442Arg	missense	Exon 12 of 12	NP_733775.1	O14770-1
	MEIS2	NM_001220482.2		c.1303G>C	p.Gly435Arg	missense	Exon 13 of 13	NP_001207411.1	O14770-4
	MEIS2	NM_170676.5		c.1303G>C	p.Gly435Arg	missense	Exon 12 of 12	NP_733776.1	O14770-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	ENST00000561208.6	TSL:1 MANE Select	c.1324G>C	p.Gly442Arg	missense	Exon 12 of 12	ENSP00000453793.1	O14770-1
	MEIS2	ENST00000338564.9	TSL:1	c.1303G>C	p.Gly435Arg	missense	Exon 13 of 13	ENSP00000341400.4	O14770-4
	MEIS2	ENST00000424352.6	TSL:1	c.*214G>C		3_prime_UTR	Exon 13 of 13	ENSP00000404185.2	O14770-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250874 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.9	L
PhyloP100		5.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.55	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.026	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.50
MutPred		0.32		Gain of solvent accessibility (P = 0.0584)
MVP		0.65
MPC		0.0082
ClinPred		0.56	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.46
Mutation Taster		=63/37	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

Other links and lift over

dbSNP: rs201588285; hg19: chr15-37184484;