2-66529844-A-G

Variant names:

• chr2-66529844-A-G
• rs3891585
• NM_002398.3:c.888+17550A>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.888+17550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,010 control chromosomes in the GnomAD database, including 29,285 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 (29285 hom., cov: 32)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS1	NM_002398.3	c.888+17550A>G		intron_variant	Intron 8 of 12	ENST00000272369.14	NP_002389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIS1	ENST00000272369.14	c.888+17550A>G		intron_variant	Intron 8 of 12	1	NM_002398.3	ENSP00000272369.8

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93699 AN: 151892 Hom.: 29265 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.617 AC: 93752 AN: 152010 Hom.: 29285 Cov.: 32 AF XY: 0.624 AC XY: 46336 AN XY: 74288

African (AFR) AF: 0.571 AC: 23672 AN: 41434

American (AMR) AF: 0.682 AC: 10435 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3470

East Asian (EAS) AF: 0.805 AC: 4163 AN: 5170

South Asian (SAS) AF: 0.783 AC: 3774 AN: 4820

European-Finnish (FIN) AF: 0.595 AC: 6283 AN: 10558

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40888 AN: 67948

Other (OTH) AF: 0.647 AC: 1362 AN: 2106

Alfa AF: 0.614 Hom.: 61931

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-0.045
Mutation Taster		=99/1	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: rs3891585; hg19: chr2-66756976; COSMIC: COSV55493209;