rs1060500654

chr2-144398981-TA-CG

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP6_Very_Strong

The NM_014795.4(ZEB2):c.2205_2206delinsCG(p.Met736Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P735P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZEB2 NM_014795.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.721

Genes affected

ZEB2 (HGNC:14881): (zinc finger E-box binding homeobox 2) The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ZEB2
• BP6: Variant 2-144398981-TA-CG is Benign according to our data. Variant chr2-144398981-TA-CG is described in ClinVar as [Likely_benign]. Clinvar id is 405332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.2205_2206delinsCG	p.Met736Val	missense_variant	8/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.2133_2134delinsCG	p.Met712Val	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.2205_2206delinsCG	p.Met736Val	missense_variant	8/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2017

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Mowat-Wilson syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1060500654; hg19: chr2-145156548;