rs1543245

Positions:

• chr15-37065309-A-G
• chr15-37065309-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561208.6(MEIS2):​c.754+18462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,070 control chromosomes in the GnomAD database, including 3,857 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 0.22 (3857 hom., cov: 33)
• Consequence: MEIS2 ENST00000561208.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.754+18462T>C		intron_variant		ENST00000561208.6	NP_733775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIS2	ENST00000561208.6	c.754+18462T>C		intron_variant		1	NM_170675.5	ENSP00000453793

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33866 AN: 151952 Hom.: 3858 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.223 AC: 33875 AN: 152070 Hom.: 3857 Cov.: 33 AF XY: 0.224 AC XY: 16669 AN XY: 74350

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.211

Alfa AF: 0.232 Hom.: 8354

Bravo AF: 0.220

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs1543245; hg19: chr15-37357510;