rs1134647

Variant names:

• chr1-214318943-G-A
• rs1134647
• NM_020197.3:c.494G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-214318943-G-A
• chr1-214318943-G-C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020197.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD2	NM_020197.3	MANE Select	c.494G>A	p.Gly165Glu	missense	Exon 5 of 12	NP_064582.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMYD2	ENST00000366957.10	TSL:1 MANE Select	c.494G>A	p.Gly165Glu	missense	Exon 5 of 12	ENSP00000355924.5
	SMYD2	ENST00000460580.5	TSL:1	n.463G>A		non_coding_transcript_exon	Exon 4 of 11
	SMYD2	ENST00000471645.5	TSL:1	n.624G>A		non_coding_transcript_exon	Exon 5 of 10

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

GnomAD2 exomes AF: 0.848 AC: 213155 AN: 251362 AF XY: 0.850

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 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

African (AFR) AF: 0.985 AC: 32990 AN: 33478

American (AMR) AF: 0.724 AC: 32367 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 21572 AN: 26130

East Asian (EAS) AF: 0.613 AC: 24338 AN: 39694

South Asian (SAS) AF: 0.812 AC: 70040 AN: 86252

European-Finnish (FIN) AF: 0.867 AC: 46313 AN: 53400

Middle Eastern (MID) AF: 0.811 AC: 4679 AN: 5768

European-Non Finnish (NFE) AF: 0.920 AC: 1022721 AN: 1111930

Other (OTH) AF: 0.886 AC: 53493 AN: 60392

GnomAD4 genome AF: 0.900 AC: 136828 AN: 152092 Hom.: 62114 Cov.: 30 AF XY: 0.890 AC XY: 66166 AN XY: 74324

African (AFR) AF: 0.981 AC: 40709 AN: 41506

American (AMR) AF: 0.790 AC: 12078 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2879 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3193 AN: 5142

South Asian (SAS) AF: 0.808 AC: 3872 AN: 4794

European-Finnish (FIN) AF: 0.860 AC: 9095 AN: 10574

Middle Eastern (MID) AF: 0.866 AC: 251 AN: 290

European-Non Finnish (NFE) AF: 0.915 AC: 62190 AN: 68004

Other (OTH) AF: 0.891 AC: 1879 AN: 2110

Alfa AF: 0.901 Hom.: 215196

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 v4.9

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
PhyloP100		4.9
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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