rs10518918

chr15-36942564-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_170675.5(MEIS2):c.977+7760T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,222 control chromosomes in the GnomAD database, including 720 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 0.065 (720 hom., cov: 32)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS2	NM_170675.5	c.977+7760T>C		intron_variant		ENST00000561208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS2	ENST00000561208.6	c.977+7760T>C		intron_variant		1	NM_170675.5

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9848 AN: 152104 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0649 AC: 9879 AN: 152222 Hom.: 720 Cov.: 32 AF XY: 0.0678 AC XY: 5047 AN XY: 74420

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.00463

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0163 Hom.: 212

Bravo AF: 0.0744

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	17
Dann	Benign	0.87

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: rs10518918; hg19: chr15-37234765;