1-85169217-T-G

Position:

• chr1-85169217-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032184.2(SYDE2):​c.2680A>C​(p.Lys894Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYDE2 NM_032184.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45

Genes affected

SYDE2 (HGNC:25841): (synapse defective Rho GTPase homolog 2) Predicted to enable GTPase activator activity. Acts upstream of or within cell migration. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYDE2	NM_032184.2	c.2680A>C	p.Lys894Gln	missense_variant	5/7	ENST00000341460.6	NP_115560.1
SYDE2	XM_017002483.2	c.2680A>C	p.Lys894Gln	missense_variant	5/7		XP_016857972.2
SYDE2	XM_017002484.3	c.2680A>C	p.Lys894Gln	missense_variant	5/8		XP_016857973.2
SYDE2	XM_047431920.1	c.2553A>C	p.Leu851Phe	missense_variant	4/4		XP_047287876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYDE2	ENST00000341460.6	c.2680A>C	p.Lys894Gln	missense_variant	5/7	5	NM_032184.2	ENSP00000340594.5
SYDE2	ENST00000696556.1	c.3271A>C	p.Lys1091Gln	missense_variant	5/7			ENSP00000512715.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jun 30, 2024

The c.2680A>C (p.K894Q) alteration is located in exon 5 (coding exon 5) of the SYDE2 gene. This alteration results from a A to C substitution at nucleotide position 2680, causing the lysine (K) at amino acid position 894 to be replaced by a glutamine (Q). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.40	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.86		Loss of methylation at K894 (P = 0.025);
MVP		0.70
MPC		0.56
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.83
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-85634900;