rs10518928

chr15-37061039-T-C

Variant summary

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

The NM_170675.5(MEIS2):c.754+22732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,140 control chromosomes in the GnomAD database, including 3,157 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 0.20 (3157 hom., cov: 32)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS2	NM_170675.5	c.754+22732A>G		intron_variant		ENST00000561208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS2	ENST00000561208.6	c.754+22732A>G		intron_variant		1	NM_170675.5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30354 AN: 152022 Hom.: 3158 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.200 AC: 30356 AN: 152140 Hom.: 3157 Cov.: 32 AF XY: 0.201 AC XY: 14954 AN XY: 74366

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.195

Alfa AF: 0.188 Hom.: 527

Bravo AF: 0.196

Asia WGS AF: 0.243 AC: 843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.5
Dann	Benign	0.78

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: rs10518928; hg19: chr15-37353240;