15-36894792-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP6_Moderate

The ENST00000424352.6(MEIS2):c.1168A>G(p.Met390Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: MEIS2 ENST00000424352.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.97

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, MEIS2
• BP6: Variant 15-36894792-T-C is Benign according to our data. Variant chr15-36894792-T-C is described in ClinVar as [Benign]. Clinvar id is 2036593.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS2	NM_170675.5	c.1147+359A>G		intron_variant		ENST00000561208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS2	ENST00000561208.6	c.1147+359A>G		intron_variant		1	NM_170675.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249576 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135402

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461406 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.14
Cadd	Benign	22
Dann	Benign	0.95
Eigen	Benign	0.051
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PROVEAN	Benign	-1.1	N;N;N;.;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.10	T;T;T;.;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T;T
Polyphen		0.0, 0.015	.;.;.;.;.;B;B
Vest4		0.66
MVP		0.98
ClinPred		0.23	T
GERP RS		5.5

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: rs372540616; hg19: chr15-37186993;