rs4625687

chr15-37072053-G-Achr15-37072053-G-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+11718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,798 control chromosomes in the GnomAD database, including 28,176 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 0.60 (28176 hom., cov: 31)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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 (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS2	NM_170675.5	c.754+11718C>T		intron_variant		ENST00000561208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS2	ENST00000561208.6	c.754+11718C>T		intron_variant		1	NM_170675.5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90821 AN: 151680 Hom.: 28178 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.598 AC: 90836 AN: 151798 Hom.: 28176 Cov.: 31 AF XY: 0.598 AC XY: 44343 AN XY: 74180

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.636

Alfa AF: 0.668 Hom.: 68830

Bravo AF: 0.593

Asia WGS AF: 0.590 AC: 2054 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	0.037
Dann	Benign	0.42

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: rs4625687; hg19: chr15-37364254;