2-66522885-T-G

Variant names:

• chr2-66522885-T-G
• rs4544423
• NM_002398.3:c.888+10591T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002398.3(MEIS1):​c.888+10591T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,094 control chromosomes in the GnomAD database, including 22,730 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 0.53 (22730 hom., cov: 33)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	NM_002398.3	MANE Select	c.888+10591T>G		intron	N/A	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.888+10591T>G		intron	N/A	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.888+10591T>G		intron	N/A	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.882+10591T>G		intron	N/A	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79984 AN: 151976 Hom.: 22715 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.526 AC: 80018 AN: 152094 Hom.: 22730 Cov.: 33 AF XY: 0.536 AC XY: 39838 AN XY: 74340

African (AFR) AF: 0.300 AC: 12446 AN: 41488

American (AMR) AF: 0.629 AC: 9615 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2242 AN: 3464

East Asian (EAS) AF: 0.780 AC: 4032 AN: 5168

South Asian (SAS) AF: 0.690 AC: 3326 AN: 4820

European-Finnish (FIN) AF: 0.593 AC: 6266 AN: 10568

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40105 AN: 67994

Other (OTH) AF: 0.573 AC: 1210 AN: 2112

Alfa AF: 0.496 Hom.: 3666

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		1.7
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: rs4544423; hg19: chr2-66750017;