rs713993044

Positions:

• chr17-43661285-G-A
• chr17-43661285-G-C
• chr17-43661285-G-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_004527.4(MEOX1):​c.250C>T​(p.Gln84Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEOX1 NM_004527.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.88

Genes affected

MEOX1 (HGNC:7013): (mesenchyme homeobox 1) This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the molecular signaling network regulating somite development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-43661285-G-A is Pathogenic according to our data. Variant chr17-43661285-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 162132.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEOX1	NM_004527.4	c.250C>T	p.Gln84Ter	stop_gained	1/3	ENST00000318579.9	NP_004518.1
MEOX1	NM_013999.4	c.250C>T	p.Gln84Ter	stop_gained	1/2		NP_054705.1
MEOX1	XM_011524818.3	c.250C>T	p.Gln84Ter	stop_gained	1/3		XP_011523120.1
MEOX1	NM_001040002.2	c.-96C>T		5_prime_UTR_variant	2/4		NP_001035091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEOX1	ENST00000318579.9	c.250C>T	p.Gln84Ter	stop_gained	1/3	1	NM_004527.4	ENSP00000321684	P1
MEOX1	ENST00000549132.2	c.250C>T	p.Gln84Ter	stop_gained	1/2	1		ENSP00000449049
MEOX1	ENST00000393661.2	c.-96C>T		5_prime_UTR_variant	2/4	3		ENSP00000377271

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Klippel-Feil syndrome 2, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 28, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.86	D
MutationTaster	Benign	1.0	A;A;D;D
Vest4		0.90
GERP RS		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs713993044; hg19: chr17-41738653;