Genetic Variant NM_197968.4:c.273A>T (chr13-19993345-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_197968.4(ZMYM2):c.273A>T(p.Glu91Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZMYM2
NM_197968.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.221

Publications

0 publications found

Variant links:

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

ZMYM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12492666).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM2	NM_197968.4	MANE Select	c.273A>T	p.Glu91Asp	missense	Exon 3 of 25	NP_932072.1	Q9UBW7-1
ZMYM2	NM_001190964.4		c.273A>T	p.Glu91Asp	missense	Exon 4 of 26	NP_001177893.1	Q9UBW7-1
ZMYM2	NM_001190965.4		c.273A>T	p.Glu91Asp	missense	Exon 3 of 25	NP_001177894.1	Q9UBW7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM2	ENST00000610343.5	TSL:1 MANE Select	c.273A>T	p.Glu91Asp	missense	Exon 3 of 25	ENSP00000479904.1	Q9UBW7-1
ZMYM2	ENST00000382871.3	TSL:1	c.273A>T	p.Glu91Asp	missense	Exon 4 of 26	ENSP00000372324.2	Q9UBW7-1
ZMYM2	ENST00000382874.6	TSL:1	c.273A>T	p.Glu91Asp	missense	Exon 4 of 26	ENSP00000372327.2	Q9UBW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.55

M_CAP

Benign

0.0046

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.22

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

REVEL

Benign

0.057

Sift

Uncertain

0.026

Sift4G

Benign

0.46

Polyphen

0.98

Vest4

0.21

MutPred

0.17

Gain of catalytic residue at K88 (P = 0.0852)

MVP

0.36

ClinPred

0.22

GERP RS

1.0

Varity_R

0.098

gMVP

0.066

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over