rs8041675

Positions:

• chr15-37050401-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.755-13442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,046 control chromosomes in the GnomAD database, including 18,159 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 0.48 (18159 hom., cov: 32)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS2	NM_170675.5	c.755-13442A>G		intron_variant		ENST00000561208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS2	ENST00000561208.6	c.755-13442A>G		intron_variant		1	NM_170675.5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73544 AN: 151928 Hom.: 18158 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.484 AC: 73558 AN: 152046 Hom.: 18159 Cov.: 32 AF XY: 0.480 AC XY: 35665 AN XY: 74300

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.491

Alfa AF: 0.523 Hom.: 46020

Bravo AF: 0.470

Asia WGS AF: 0.426 AC: 1480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.79

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: rs8041675; hg19: chr15-37342602;