rs713993044

Variant names:

• chr17-43661285-G-A
• rs713993044
• NM_004527.4:c.250C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_004527.4(MEOX1):​c.250C>T​(p.Gln84*) 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
• Publications: 1 publications found

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]

MEOX1 Gene-Disease associations (from GenCC):

• Klippel-Feil syndrome 2, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• isolated Klippel-Feil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 162132.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX1	NM_004527.4	MANE Select	c.250C>T	p.Gln84*	stop_gained	Exon 1 of 3	NP_004518.1
	MEOX1	NM_013999.4		c.250C>T	p.Gln84*	stop_gained	Exon 1 of 2	NP_054705.1
	MEOX1	NM_001040002.2		c.-96C>T		5_prime_UTR	Exon 2 of 4	NP_001035091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX1	ENST00000318579.9	TSL:1 MANE Select	c.250C>T	p.Gln84*	stop_gained	Exon 1 of 3	ENSP00000321684.4
	MEOX1	ENST00000549132.2	TSL:1	c.250C>T	p.Gln84*	stop_gained	Exon 1 of 2	ENSP00000449049.2
	MEOX1	ENST00000393661.2	TSL:3	c.-96C>T		5_prime_UTR	Exon 2 of 4	ENSP00000377271.2

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

Sep 28, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.9
Vest4		0.90
GERP RS		4.7
PromoterAI		-0.050	Neutral
Mutation Taster		=16/184	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs713993044; hg19: chr17-41738653;