chr13-19993408-TGTAA-T

Variant names:

• chr13-19993408-TGTAA-T
• NM_197968.4:c.339_342delAAGT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_197968.4(ZMYM2):​c.339_342delAAGT​(p.Ser114ArgfsTer51) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYM2 NM_197968.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.24
• Publications: 0 publications found

Genes affected

ZMYM2 (HGNC:12989): (zinc finger MYM-type containing 2) The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

ZMYM2 Gene-Disease associations (from GenCC):

• neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Franklin by Genoox, Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 12 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 13-19993408-TGTAA-T is Pathogenic according to our data. Variant chr13-19993408-TGTAA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3767150.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197968.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM2	NM_197968.4	MANE Select	c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 3 of 25	NP_932072.1	Q9UBW7-1
	ZMYM2	NM_001190964.4		c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 4 of 26	NP_001177893.1	Q9UBW7-1
	ZMYM2	NM_001190965.4		c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 3 of 25	NP_001177894.1	Q9UBW7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM2	ENST00000610343.5	TSL:1 MANE Select	c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 3 of 25	ENSP00000479904.1	Q9UBW7-1
	ZMYM2	ENST00000382871.3	TSL:1	c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 4 of 26	ENSP00000372324.2	Q9UBW7-1
	ZMYM2	ENST00000382874.6	TSL:1	c.339_342delAAGT	p.Ser114ArgfsTer51	frameshift	Exon 4 of 26	ENSP00000372327.2	Q9UBW7-1

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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

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

Other links and lift over

hg19: chr13-20567548;