rs2300478

Variant names:

• chr2-66554321-T-G
• rs2300478
• NM_002398.3:c.965+6302T>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.965+6302T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,136 control chromosomes in the GnomAD database, including 3,676 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 0.21 (3676 hom., cov: 33)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 62 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]

LOC124900511 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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.965+6302T>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.965+6302T>G		intron	N/A	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.965+6302T>G		intron	N/A	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.959+6302T>G		intron	N/A	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32352 AN: 152018 Hom.: 3679 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.213 AC: 32341 AN: 152136 Hom.: 3676 Cov.: 33 AF XY: 0.214 AC XY: 15929 AN XY: 74358

African (AFR) AF: 0.129 AC: 5370 AN: 41522

American (AMR) AF: 0.208 AC: 3181 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5166

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4816

European-Finnish (FIN) AF: 0.246 AC: 2608 AN: 10588

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16785 AN: 67982

Other (OTH) AF: 0.229 AC: 484 AN: 2110

Alfa AF: 0.238 Hom.: 19824

Bravo AF: 0.208

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.31
PhyloP100		1.8
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: rs2300478; hg19: chr2-66781453;