rs8041675

Variant names:

• chr15-37050401-T-C
• rs8041675
• NM_170675.5:c.755-13442A>G

Variant summary

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

The NM_170675.5(MEIS2):​c.755-13442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,046 control chromosomes in the GnomAD database, including 18,159 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 0.48 (18159 hom., cov: 32)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.755-13442A>G		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.755-13442A>G		intron_variant	Intron 7 of 11	1	NM_170675.5	ENSP00000453793.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73544 AN: 151928 Hom.: 18158 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.484 AC: 73558 AN: 152046 Hom.: 18159 Cov.: 32 AF XY: 0.480 AC XY: 35665 AN XY: 74300

African (AFR) AF: 0.423 AC: 17522 AN: 41464

American (AMR) AF: 0.395 AC: 6036 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1784 AN: 5166

South Asian (SAS) AF: 0.561 AC: 2705 AN: 4824

European-Finnish (FIN) AF: 0.492 AC: 5182 AN: 10542

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36469 AN: 67988

Other (OTH) AF: 0.491 AC: 1034 AN: 2106

Alfa AF: 0.513 Hom.: 66140

Bravo AF: 0.470

Asia WGS AF: 0.426 AC: 1480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-0.63
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: rs8041675; hg19: chr15-37342602;