15-37094306-G-T

Variant names:

• chr15-37094306-G-T
• rs1464284
• NM_170675.5:c.489+221C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170675.5(MEIS2):​c.489+221C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,784 control chromosomes in the GnomAD database, including 24,121 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 0.56 (24121 hom., cov: 30)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 7 publications found

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]

MEIS2 Gene-Disease associations (from GenCC):

• cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.489+221C>A		intron_variant	Intron 5 of 11	ENST00000561208.6	NP_733775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIS2	ENST00000561208.6	c.489+221C>A		intron_variant	Intron 5 of 11	1	NM_170675.5	ENSP00000453793.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85239 AN: 151666 Hom.: 24093 Cov.: 30

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.562 AC: 85320 AN: 151784 Hom.: 24121 Cov.: 30 AF XY: 0.569 AC XY: 42223 AN XY: 74178

African (AFR) AF: 0.548 AC: 22676 AN: 41374

American (AMR) AF: 0.610 AC: 9309 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1830 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3097 AN: 5148

South Asian (SAS) AF: 0.629 AC: 3020 AN: 4804

European-Finnish (FIN) AF: 0.682 AC: 7187 AN: 10536

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36424 AN: 67890

Other (OTH) AF: 0.533 AC: 1124 AN: 2108

Alfa AF: 0.539 Hom.: 36605

Bravo AF: 0.554

Asia WGS AF: 0.619 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.62
PhyloP100		-0.15
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1464284; hg19: chr15-37386507;