Variant chr1-214318943-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020197.3(SMYD2):c.494G>A(p.Gly165Glu) variant causes a missense change. The variant allele was found at a frequency of 0.896 in 1,613,858 control chromosomes in the GnomAD database, including 651,340 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.90 ( 62114 hom., cov: 30)

Exomes 𝑓: 0.90 ( 589226 hom. )

Consequence

SMYD2
NM_020197.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.95

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.062223E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMYD2	NM_020197.3 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	5/12	ENST00000366957.10
SMYD2	XM_047425700.1 linkuse as main transcript	c.242G>A	p.Gly81Glu	missense_variant	4/11
SMYD2	XM_047425702.1 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD2	ENST00000366957.10 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	5/12	1	NM_020197.3	P1	Q9NRG4-1
SMYD2	ENST00000460580.5 linkuse as main transcript	n.463G>A		non_coding_transcript_exon_variant	4/11	1
SMYD2	ENST00000471645.5 linkuse as main transcript	n.624G>A		non_coding_transcript_exon_variant	5/10	1
SMYD2	ENST00000491455.5 linkuse as main transcript	n.647G>A		non_coding_transcript_exon_variant	5/11	2

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136720

AN:

151974

Hom.:

62062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.981

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.790

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.865

Gnomad NFE

AF:

0.915

Gnomad OTH

AF:

0.889

GnomAD3 exomes

AF:

0.848

AC:

213155

AN:

251362

Hom.:

91741

AF XY:

0.850

AC XY:

115534

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.983

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.826

Gnomad EAS exome

AF:

0.619

Gnomad SAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.865

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.895

AC:

1308513

AN:

1461766

Hom.:

589226

Cov.:

AF XY:

0.892

AC XY:

649009

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.985

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.826

Gnomad4 EAS exome

AF:

0.613

Gnomad4 SAS exome

AF:

0.812

Gnomad4 FIN exome

AF:

0.867

Gnomad4 NFE exome

AF:

0.920

Gnomad4 OTH exome

AF:

0.886

GnomAD4 genome

AF:

0.900

AC:

136828

AN:

152092

Hom.:

62114

Cov.:

AF XY:

0.890

AC XY:

66166

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.981

Gnomad4 AMR

AF:

0.790

Gnomad4 ASJ

AF:

0.830

Gnomad4 EAS

AF:

0.621

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.860

Gnomad4 NFE

AF:

0.915

Gnomad4 OTH

AF:

0.891

Alfa

AF:

0.900

Hom.:

154398

Bravo

AF:

0.896

TwinsUK

AF:

0.917

AC:

3399

ALSPAC

AF:

0.923

AC:

3558

ESP6500AA

AF:

0.979

AC:

4314

ESP6500EA

AF:

0.917

AC:

7890

ExAC

AF:

0.858

AC:

104152

Asia WGS

AF:

0.773

AC:

2691

AN:

3478

EpiCase

AF:

0.904

EpiControl

AF:

0.907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.39

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.12

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

2.7

REVEL

Benign

0.17

Sift

Benign

0.83

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.022

MPC

0.36

ClinPred

0.0079

GERP RS

5.5

Varity_R

0.18

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over