Variant chr1-214324674-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_020197.3(SMYD2):c.568G>A(p.Glu190Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SMYD2
NM_020197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33

Variant links:

Genes affected

SMYD2 (HGNC:20982): (SET and MYND domain containing 2) SET domain-containing proteins, such as SMYD2, catalyze lysine methylation (Brown et al., 2006 [PubMed 16805913]).[supplied by OMIM, Nov 2008]

SMYD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a mutagenesis_site Strongly reduces methyltransferase activity on p53/TP53. (size 0) in uniprot entity SMYD2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMYD2	NM_020197.3 linkuse as main transcript	c.568G>A	p.Glu190Lys	missense_variant	6/12	ENST00000366957.10
SMYD2	XM_047425700.1 linkuse as main transcript	c.316G>A	p.Glu106Lys	missense_variant	5/11
SMYD2	XM_047425702.1 linkuse as main transcript	c.568G>A	p.Glu190Lys	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD2	ENST00000366957.10 linkuse as main transcript	c.568G>A	p.Glu190Lys	missense_variant	6/12	1	NM_020197.3	P1	Q9NRG4-1
SMYD2	ENST00000460580.5 linkuse as main transcript	n.537G>A		non_coding_transcript_exon_variant	5/11	1
SMYD2	ENST00000471645.5 linkuse as main transcript	n.698G>A		non_coding_transcript_exon_variant	6/10	1
SMYD2	ENST00000491455.5 linkuse as main transcript	n.721G>A		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250536

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460904

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.568G>A (p.E190K) alteration is located in exon 6 (coding exon 6) of the SMYD2 gene. This alteration results from a G to A substitution at nucleotide position 568, causing the glutamic acid (E) at amino acid position 190 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Benign

0.062

Polyphen

1.0

Vest4

0.84

MutPred

0.42

Gain of ubiquitination at E190 (P = 0.0104);

MVP

0.64

MPC

0.73

ClinPred

0.84

GERP RS

5.3

Varity_R

0.92

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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