chr2-66537865-A-G

Variant names:

• chr2-66537865-A-G
• rs10865355
• NM_002398.3:c.889-10078A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002398.3(MEIS1):​c.889-10078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,064 control chromosomes in the GnomAD database, including 29,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29380 hom., cov: 33)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	NM_002398.3	MANE Select	c.889-10078A>G		intron	N/A	NP_002389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	ENST00000272369.14	TSL:1 MANE Select	c.889-10078A>G		intron	N/A	ENSP00000272369.8
	MEIS1	ENST00000488550.5	TSL:1	c.889-10078A>G		intron	N/A	ENSP00000475161.1
	MEIS1	ENST00000398506.6	TSL:5	c.883-10078A>G		intron	N/A	ENSP00000381518.2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93893 AN: 151946 Hom.: 29361 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 93945 AN: 152064 Hom.: 29380 Cov.: 33 AF XY: 0.625 AC XY: 46463 AN XY: 74340

African (AFR) AF: 0.575 AC: 23829 AN: 41468

American (AMR) AF: 0.682 AC: 10427 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3466

East Asian (EAS) AF: 0.810 AC: 4191 AN: 5174

South Asian (SAS) AF: 0.785 AC: 3783 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6279 AN: 10566

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.601 AC: 40876 AN: 67960

Other (OTH) AF: 0.649 AC: 1373 AN: 2116

Alfa AF: 0.617 Hom.: 54995

Bravo AF: 0.625

Asia WGS AF: 0.759 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.29
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10865355; hg19: chr2-66764997;