NM_170675.5:c.754+11718C>T

Variant names:

• chr15-37072053-G-A
• rs4625687
• NM_170675.5:c.754+11718C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.754+11718C>T		intron_variant	Intron 7 of 11	ENST00000561208.6	NP_733775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIS2	ENST00000561208.6	c.754+11718C>T		intron_variant	Intron 7 of 11	1	NM_170675.5	ENSP00000453793.1

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

African (AFR) AF: 0.413 AC: 17113 AN: 41392

American (AMR) AF: 0.669 AC: 10184 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2337 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2780 AN: 5140

South Asian (SAS) AF: 0.678 AC: 3260 AN: 4806

European-Finnish (FIN) AF: 0.637 AC: 6721 AN: 10550

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.679 AC: 46088 AN: 67910

Other (OTH) AF: 0.636 AC: 1341 AN: 2108

Alfa AF: 0.657 Hom.: 141887

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
PhyloP100		-0.57
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: rs4625687; hg19: chr15-37364254;