Variant chr1-214314777-A-G 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.253A>G(p.Met85Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SMYD2
NM_020197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

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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=0.1544284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMYD2	NM_020197.3 linkuse as main transcript	c.253A>G	p.Met85Val	missense_variant	3/12	ENST00000366957.10
SMYD2	XM_047425700.1 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	2/11
SMYD2	XM_047425702.1 linkuse as main transcript	c.253A>G	p.Met85Val	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD2	ENST00000366957.10 linkuse as main transcript	c.253A>G	p.Met85Val	missense_variant	3/12	1	NM_020197.3	P1	Q9NRG4-1
SMYD2	ENST00000460580.5 linkuse as main transcript	n.222A>G		non_coding_transcript_exon_variant	2/11	1
SMYD2	ENST00000471645.5 linkuse as main transcript	n.383A>G		non_coding_transcript_exon_variant	3/10	1
SMYD2	ENST00000491455.5 linkuse as main transcript	n.406A>G		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251432

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135890

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:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727172

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

May 26, 2023

The c.253A>G (p.M85V) alteration is located in exon 3 (coding exon 3) of the SMYD2 gene. This alteration results from a A to G substitution at nucleotide position 253, causing the methionine (M) at amino acid position 85 to be replaced by a valine (V). 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

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0085

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.10

MutationTaster

Benign

0.86

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Benign

0.90

Sift4G

Benign

0.53

Polyphen

0.17

Vest4

0.30

MutPred

0.49

Gain of catalytic residue at M85 (P = 0.0484);

MVP

0.32

MPC

0.28

ClinPred

0.090

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.57

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