rs1568679

Variant names:

• chr15-37057601-T-C
• rs1568679
• NM_170675.5:c.755-20642A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_170675.5(MEIS2):​c.755-20642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,102 control chromosomes in the GnomAD database, including 821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.098 (821 hom., cov: 32)
• Consequence: MEIS2 NM_170675.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.41
• Publications: 16 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=-0.3).
• BP6: Variant 15-37057601-T-C is Benign according to our data. Variant chr15-37057601-T-C is described in ClinVar as Benign. ClinVar VariationId is 1296892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS2	NM_170675.5	c.755-20642A>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.755-20642A>G		intron_variant	Intron 7 of 11	1	NM_170675.5	ENSP00000453793.1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14816 AN: 151984 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0977 AC: 14859 AN: 152102 Hom.: 821 Cov.: 32 AF XY: 0.100 AC XY: 7465 AN XY: 74338

African (AFR) AF: 0.102 AC: 4231 AN: 41494

American (AMR) AF: 0.115 AC: 1758 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.145 AC: 749 AN: 5168

South Asian (SAS) AF: 0.0567 AC: 273 AN: 4812

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10572

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5649 AN: 67990

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0888 Hom.: 2584

Bravo AF: 0.0953

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29518216) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		3.4
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: rs1568679; hg19: chr15-37349802;