rs1543245

Variant names:

• chr15-37065309-A-G
• rs1543245
• NM_170675.5:c.754+18462T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-37065309-A-G
• chr15-37065309-A-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+18462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,070 control chromosomes in the GnomAD database, including 3,857 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 0.22 (3857 hom., cov: 33)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.754+18462T>C		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+18462T>C		intron_variant	Intron 7 of 11	1	NM_170675.5	ENSP00000453793.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33866 AN: 151952 Hom.: 3858 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.223 AC: 33875 AN: 152070 Hom.: 3857 Cov.: 33 AF XY: 0.224 AC XY: 16669 AN XY: 74350

African (AFR) AF: 0.212 AC: 8799 AN: 41496

American (AMR) AF: 0.191 AC: 2915 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1644 AN: 5164

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4820

European-Finnish (FIN) AF: 0.212 AC: 2241 AN: 10592

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15815 AN: 67940

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.230 Hom.: 18033

Bravo AF: 0.220

Asia WGS AF: 0.253 AC: 879 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	7.4
DANN	Benign	0.55
PhyloP100		-0.95
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: rs1543245; hg19: chr15-37357510;