chr5-139813626-G-C

Variant names:

• chr5-139813626-G-C
• rs201061729
• NM_032289.4:c.689G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032289.4(PSD2):​c.689G>C​(p.Arg230Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R230H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSD2 NM_032289.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05
• Publications: 3 publications found

Genes affected

PSD2 (HGNC:19092): (pleckstrin and Sec7 domain containing 2) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Predicted to be located in cleavage furrow and ruffle membrane. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42104405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD2	NM_032289.4	c.689G>C	p.Arg230Pro	missense_variant	Exon 3 of 15	ENST00000274710.4	NP_115665.1
PSD2	XM_017009976.2	c.689G>C	p.Arg230Pro	missense_variant	Exon 4 of 16		XP_016865465.1
PSD2	XM_017009977.2	c.689G>C	p.Arg230Pro	missense_variant	Exon 4 of 16		XP_016865466.1
PSD2	XM_047417829.1	c.689G>C	p.Arg230Pro	missense_variant	Exon 3 of 15		XP_047273785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD2	ENST00000274710.4	c.689G>C	p.Arg230Pro	missense_variant	Exon 3 of 15	1	NM_032289.4	ENSP00000274710.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.57
MutPred		0.29		Loss of MoRF binding (P = 0.0011);
MVP		0.36
MPC		0.21
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.66
Mutation Taster		=43/57	disease causing

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: rs201061729; hg19: chr5-139193211;