NM_170675.5:c.754+3361G>A

Variant names:

• chr15-37080410-C-T
• rs4244559
• NM_170675.5:c.754+3361G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_170675.5(MEIS2):​c.754+3361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,918 control chromosomes in the GnomAD database, including 33,612 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 0.66 (33612 hom., cov: 31)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	NM_170675.5	MANE Select	c.754+3361G>A		intron	N/A	NP_733775.1
	MEIS2	NM_001220482.2		c.754+3361G>A		intron	N/A	NP_001207411.1
	MEIS2	NM_170676.5		c.754+3361G>A		intron	N/A	NP_733776.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS2	ENST00000561208.6	TSL:1 MANE Select	c.754+3361G>A		intron	N/A	ENSP00000453793.1
	MEIS2	ENST00000338564.9	TSL:1	c.754+3361G>A		intron	N/A	ENSP00000341400.4
	MEIS2	ENST00000424352.6	TSL:1	c.754+3361G>A		intron	N/A	ENSP00000404185.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100781 AN: 151798 Hom.: 33587 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.664 AC: 100854 AN: 151918 Hom.: 33612 Cov.: 31 AF XY: 0.667 AC XY: 49521 AN XY: 74228

African (AFR) AF: 0.603 AC: 24953 AN: 41404

American (AMR) AF: 0.703 AC: 10741 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2312 AN: 3466

East Asian (EAS) AF: 0.657 AC: 3381 AN: 5148

South Asian (SAS) AF: 0.682 AC: 3289 AN: 4820

European-Finnish (FIN) AF: 0.772 AC: 8158 AN: 10564

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45751 AN: 67924

Other (OTH) AF: 0.657 AC: 1387 AN: 2110

Alfa AF: 0.671 Hom.: 37127

Bravo AF: 0.657

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		2.4
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: rs4244559; hg19: chr15-37372611;