15-37006950-C-T

Variant names:

• chr15-37006950-C-T
• rs4924116
• NM_170675.5:c.900+29864G>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.900+29864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,226 control chromosomes in the GnomAD database, including 1,749 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 0.12 (1749 hom., cov: 33)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 3 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: Illumina, Ambry Genetics
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170675.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	NM_170675.5	MANE Select	c.900+29864G>A		intron	N/A	NP_733775.1	O14770-1
	MEIS2	NM_001220482.2		c.900+29864G>A		intron	N/A	NP_001207411.1	O14770-4
	MEIS2	NM_170676.5		c.900+29864G>A		intron	N/A	NP_733776.1	O14770-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	ENST00000561208.6	TSL:1 MANE Select	c.900+29864G>A		intron	N/A	ENSP00000453793.1	O14770-1
	MEIS2	ENST00000338564.9	TSL:1	c.900+29864G>A		intron	N/A	ENSP00000341400.4	O14770-4
	MEIS2	ENST00000424352.6	TSL:1	c.900+29864G>A		intron	N/A	ENSP00000404185.2	O14770-2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17868 AN: 152108 Hom.: 1731 Cov.: 33

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.118 AC: 17914 AN: 152226 Hom.: 1749 Cov.: 33 AF XY: 0.123 AC XY: 9134 AN XY: 74428

African (AFR) AF: 0.0623 AC: 2587 AN: 41534

American (AMR) AF: 0.329 AC: 5025 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1552 AN: 5168

South Asian (SAS) AF: 0.122 AC: 587 AN: 4822

European-Finnish (FIN) AF: 0.0921 AC: 977 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0919 AC: 6251 AN: 68024

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.134 Hom.: 467

Bravo AF: 0.141

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.044
DANN	Benign	0.75
PhyloP100		-1.3
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: rs4924116; hg19: chr15-37299151;