2-66522885-T-G

Position:

• chr2-66522885-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002398.3(MEIS1):​c.888+10591T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,094 control chromosomes in the GnomAD database, including 22,730 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 0.53 (22730 hom., cov: 33)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

Genes affected

MEIS1 (HGNC:7000): (Meis homeobox 1) Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS1	NM_002398.3	c.888+10591T>G		intron_variant		ENST00000272369.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS1	ENST00000272369.14	c.888+10591T>G		intron_variant		1	NM_002398.3	P2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79984 AN: 151976 Hom.: 22715 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.526 AC: 80018 AN: 152094 Hom.: 22730 Cov.: 33 AF XY: 0.536 AC XY: 39838 AN XY: 74340

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.573

Alfa AF: 0.502 Hom.: 3038

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs4544423; hg19: chr2-66750017;