Variant chr1-214281286-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020197.3(SMYD2):c.32G>C(p.Arg11Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000561 in 1,328,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

SMYD2
NM_020197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1753113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMYD2	NM_020197.3 linkuse as main transcript	c.32G>C	p.Arg11Pro	missense_variant	1/12	ENST00000366957.10
SMYD2	XM_047425702.1 linkuse as main transcript	c.32G>C	p.Arg11Pro	missense_variant	1/9
SMYD2	XM_047425700.1 linkuse as main transcript	c.-157G>C		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD2	ENST00000366957.10 linkuse as main transcript	c.32G>C	p.Arg11Pro	missense_variant	1/12	1	NM_020197.3	P1	Q9NRG4-1
SMYD2	ENST00000460580.5 linkuse as main transcript	n.65G>C		non_coding_transcript_exon_variant	1/11	1
SMYD2	ENST00000471645.5 linkuse as main transcript	n.162G>C		non_coding_transcript_exon_variant	1/10	1
SMYD2	ENST00000491455.5 linkuse as main transcript	n.185G>C		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes

AF:

0.000265

AC:

AN:

150758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

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:

0.000459

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

90938

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

54058

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:

0.000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000599

AC:

706

AN:

1177970

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

326

AN XY:

570900

show subpopulations

Gnomad4 AFR exome

AF:

0.000125

Gnomad4 AMR exome

AF:

0.0000666

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000718

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000265

AC:

AN:

150868

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

73726

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.000459

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.000283

ExAC

AF:

0.000180

AC:

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

Feb 27, 2024

The c.32G>C (p.R11P) alteration is located in exon 1 (coding exon 1) of the SMYD2 gene. This alteration results from a G to C substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a proline (P). 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

0.57

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

0.18

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.18

Sift

Uncertain

0.010

Sift4G

Benign

0.13

Polyphen

0.94

Vest4

0.65

MVP

0.46

MPC

0.70

ClinPred

0.33

GERP RS

2.8

Varity_R

0.93

gMVP

0.89

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