1-214305200-T-A

Position:

• chr1-214305200-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020197.3(SMYD2):​c.187T>A​(p.Ser63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SMYD2 NM_020197.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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 (HGNC:):

ACMG classification

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=0.23163506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD2	NM_020197.3	c.187T>A	p.Ser63Thr	missense_variant	2/12	ENST00000366957.10	NP_064582.2
SMYD2	XM_047425702.1	c.187T>A	p.Ser63Thr	missense_variant	2/9		XP_047281658.1
SMYD2	XM_047425700.1	c.-15-9562T>A		intron_variant			XP_047281656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD2	ENST00000366957.10	c.187T>A	p.Ser63Thr	missense_variant	2/12	1	NM_020197.3	ENSP00000355924.5
SMYD2	ENST00000471645.5	n.317T>A		non_coding_transcript_exon_variant	2/10	1
SMYD2	ENST00000460580.5	n.207-9562T>A		intron_variant		1
SMYD2	ENST00000491455.5	n.340T>A		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.187T>A (p.S63T) alteration is located in exon 2 (coding exon 2) of the SMYD2 gene. This alteration results from a T to A substitution at nucleotide position 187, causing the serine (S) at amino acid position 63 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.081
Sift	Benign	0.13	T
Sift4G	Benign	0.45	T
Polyphen		0.20	B
Vest4		0.37
MutPred		0.42		Loss of disorder (P = 0.1678);
MVP		0.40
MPC		0.26
ClinPred		0.45	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-214478543;