rs9308433

Variant names:

• chr1-214283666-T-C
• rs9308433
• NM_020197.3:c.173+2239T>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.173+2239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,994 control chromosomes in the GnomAD database, including 13,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13997 hom., cov: 32)
• Consequence: SMYD2 NM_020197.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 7 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD2	NM_020197.3	c.173+2239T>C		intron_variant	Intron 1 of 11	ENST00000366957.10	NP_064582.2
SMYD2	XM_047425700.1	c.-16+2239T>C		intron_variant	Intron 1 of 10		XP_047281656.1
SMYD2	XM_047425702.1	c.173+2239T>C		intron_variant	Intron 1 of 8		XP_047281658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD2	ENST00000366957.10	c.173+2239T>C		intron_variant	Intron 1 of 11	1	NM_020197.3	ENSP00000355924.5
SMYD2	ENST00000460580.5	n.206+2239T>C		intron_variant	Intron 1 of 10	1
SMYD2	ENST00000471645.5	n.303+2239T>C		intron_variant	Intron 1 of 9	1
SMYD2	ENST00000491455.5	n.326+2239T>C		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62912 AN: 151876 Hom.: 13971 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62987 AN: 151994 Hom.: 13997 Cov.: 32 AF XY: 0.408 AC XY: 30286 AN XY: 74294

African (AFR) AF: 0.574 AC: 23756 AN: 41414

American (AMR) AF: 0.333 AC: 5081 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3472

East Asian (EAS) AF: 0.0632 AC: 328 AN: 5186

South Asian (SAS) AF: 0.368 AC: 1771 AN: 4818

European-Finnish (FIN) AF: 0.344 AC: 3636 AN: 10560

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26322 AN: 67962

Other (OTH) AF: 0.358 AC: 753 AN: 2106

Alfa AF: 0.390 Hom.: 42572

Bravo AF: 0.422

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9308433; hg19: chr1-214457009;