1-214332028-G-T

Position:

• chr1-214332028-G-T

Variant summary

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

The NM_020197.3(SMYD2):​c.948G>T​(p.Glu316Asp) 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. 12/21 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: 1.65

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=0.18209258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMYD2	NM_020197.3	c.948G>T	p.Glu316Asp	missense_variant	10/12	ENST00000366957.10	NP_064582.2
SMYD2	XM_047425700.1	c.696G>T	p.Glu232Asp	missense_variant	9/11		XP_047281656.1
SMYD2	XM_047425702.1	c.816+1750G>T		intron_variant			XP_047281658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMYD2	ENST00000366957.10	c.948G>T	p.Glu316Asp	missense_variant	10/12	1	NM_020197.3	ENSP00000355924.5
SMYD2	ENST00000416415.2	c.105G>T	p.Glu35Asp	missense_variant	2/3	5		ENSP00000409822.2

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

Aug 01, 2024

The c.948G>T (p.E316D) alteration is located in exon 10 (coding exon 10) of the SMYD2 gene. This alteration results from a G to T substitution at nucleotide position 948, causing the glutamic acid (E) at amino acid position 316 to be replaced by an aspartic acid (D). 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	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.056	T;T
Polyphen		0.28	B;.
Vest4		0.60
MutPred		0.37		Gain of ubiquitination at K312 (P = 0.1025);.;
MVP		0.22
MPC		0.27
ClinPred		0.86	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-214505371;