rs7511739

Variant names:

• chr1-85156774-G-A
• rs7511739
• XM_017002483.2:c.*2358C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017002483.2(SYDE2):​c.*2358C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,020 control chromosomes in the GnomAD database, including 2,537 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 0.18 (2537 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SYDE2 XM_017002483.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 6 publications found

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]

SYDE2 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000296416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYDE2	XM_017002483.2	c.*2358C>T		3_prime_UTR_variant	Exon 7 of 7		XP_016857972.2
SYDE2	NM_032184.2	c.*1976C>T		downstream_gene_variant		ENST00000341460.6	NP_115560.1
SYDE2	XM_017002484.3	c.*2509C>T		downstream_gene_variant			XP_016857973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296416	ENST00000739550.1	n.96+13665G>A		intron_variant	Intron 1 of 2
ENSG00000296416	ENST00000739551.1	n.78+13665G>A		intron_variant	Intron 1 of 1
SYDE2	ENST00000341460.6	c.*1976C>T		downstream_gene_variant		5	NM_032184.2	ENSP00000340594.5
SYDE2	ENST00000696556.1	c.*1976C>T		downstream_gene_variant				ENSP00000512715.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27216 AN: 151904 Hom.: 2530 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.179 AC: 27231 AN: 152020 Hom.: 2537 Cov.: 33 AF XY: 0.179 AC XY: 13272 AN XY: 74342

African (AFR) AF: 0.156 AC: 6472 AN: 41450

American (AMR) AF: 0.230 AC: 3509 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5178

South Asian (SAS) AF: 0.242 AC: 1169 AN: 4828

European-Finnish (FIN) AF: 0.139 AC: 1467 AN: 10542

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12125 AN: 67958

Other (OTH) AF: 0.168 AC: 353 AN: 2102

Alfa AF: 0.184 Hom.: 1725

Bravo AF: 0.189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.45
PhyloP100		0.042

Splicing

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

Other links and lift over

dbSNP: rs7511739; hg19: chr1-85622457;