2-66568750-G-A

Position:

• chr2-66568750-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002398.3(MEIS1):​c.1108G>A​(p.Ala370Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEIS1 NM_002398.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27519011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS1	NM_002398.3	c.1108G>A	p.Ala370Thr	missense_variant	11/13	ENST00000272369.14	NP_002389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIS1	ENST00000272369.14	c.1108G>A	p.Ala370Thr	missense_variant	11/13	1	NM_002398.3	ENSP00000272369	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.1108G>A (p.A370T) alteration is located in exon 11 (coding exon 11) of the MEIS1 gene. This alteration results from a G to A substitution at nucleotide position 1108, causing the alanine (A) at amino acid position 370 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;T;D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	0.34	N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.040	N;.;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.20	T;.;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.075	B;.;P;B
Vest4		0.43
MutPred		0.21		Gain of phosphorylation at A370 (P = 0.0328);Gain of phosphorylation at A370 (P = 0.0328);.;.;
MVP		0.67
MPC		0.99
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-66795882; COSMIC: COSV55487480; COSMIC: COSV55487480;