1-214318943-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020197.3(SMYD2):​c.494G>C​(p.Gly165Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 30)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083951324).

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>C	p.Gly165Ala	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>C	p.Gly165Ala	missense	Exon 5 of 12	ENSP00000355924.5
	SMYD2	ENST00000460580.5	TSL:1	n.463G>C		non_coding_transcript_exon	Exon 4 of 11
	SMYD2	ENST00000471645.5	TSL:1	n.624G>C		non_coding_transcript_exon	Exon 5 of 10

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.13
Sift	Benign	0.11	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.065
MutPred		0.34		Gain of catalytic residue at G165 (P = 0.0407)
MVP		0.36
MPC		0.30
ClinPred		0.43	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.38
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;