Variant 13-19993526-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_197968.4(ZMYM2):c.454G>C(p.Asp152His) variant causes a missense change. The variant allele was found at a frequency of 0.00364 in 1,613,978 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

ZMYM2
NM_197968.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.09

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006703675).

BP6

Variant 13-19993526-G-C is Benign according to our data. Variant chr13-19993526-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 710811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00313 (476/152286) while in subpopulation NFE AF= 0.00516 (351/68020). AF 95% confidence interval is 0.00471. There are 3 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM2	NM_197968.4 link	c.454G>C	p.Asp152His	missense_variant	3/25	ENST00000610343.5	NP_932072.1	Q9UBW7-1A0A024RDS3A8K126

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYM2	ENST00000610343.5 link	c.454G>C	p.Asp152His	missense_variant	3/25	1	NM_197968.4	ENSP00000479904.1		Q9UBW7-1

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00331

AC:

826

AN:

249816

Hom.:

AF XY:

0.00334

AC XY:

452

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.000580

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00458

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00369

AC:

5397

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2675

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00627

Gnomad4 NFE exome

AF:

0.00423

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.00313

AC:

476

AN:

152286

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00450

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000467

AC:

ESP6500EA

AF:

0.00422

AC:

ExAC

AF:

0.00342

AC:

415

EpiCase

AF:

0.00447

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	ZMYM2: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;.;.;D

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.0

M;M;M;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.1

.;N;N;.

REVEL

Benign

0.098

Sift

Uncertain

0.0060

.;D;D;.

Sift4G

Uncertain

0.025

D;D;D;T

Polyphen

0.73

P;P;P;.

Vest4

0.35

MVP

0.31

ClinPred

0.035

GERP RS

5.4

Varity_R

0.12

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over