rs1134647

chr1-214318943-G-Achr1-214318943-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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]

ACMG classification

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	UniProt
SMYD2	NM_020197.3	c.494G>A	p.Gly165Glu	missense_variant	5/12	ENST00000366957.10
SMYD2	XM_047425700.1	c.242G>A	p.Gly81Glu	missense_variant	4/11
SMYD2	XM_047425702.1	c.494G>A	p.Gly165Glu	missense_variant	5/9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136720 AN: 151974 Hom.: 62062 Cov.: 30

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

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.: 50 AF XY: 0.892 AC XY: 649009 AN XY: 727184

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.: 30 AF XY: 0.890 AC XY: 66166 AN XY: 74324

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	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	14
Dann	Benign	0.39
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.4	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.17
Sift	Benign	0.83	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.36
ClinPred		0.0079	T
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

Other links and lift over

dbSNP: rs1134647; hg19: chr1-214492286; COSMIC: COSV65291854;