chr20-59886842-A-T

Variant names:

• chr20-59886842-A-T
• rs193921008
• NM_014258.4:c.2365-8T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014258.4(SYCP2):​c.2365-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,411,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SYCP2 NM_014258.4 splice_region, intron
• Scores: Splicing: ADA: 0.007953
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 0 publications found

Genes affected

SYCP2 (HGNC:11490): (synaptonemal complex protein 2) The synaptonemal complex is a proteinaceous structure that links homologous chromosomes during the prophase of meiosis. The protein encoded by this gene is a major component of the synaptonemal complex and may bind DNA at scaffold attachment regions. The encoded protein requires synaptonemal complex protein 3, but not 1, for inclusion in the synaptonemal complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2	NM_014258.4	c.2365-8T>A		splice_region_variant, intron_variant	Intron 24 of 44	ENST00000357552.8	NP_055073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2	ENST00000357552.8	c.2365-8T>A		splice_region_variant, intron_variant	Intron 24 of 44	1	NM_014258.4	ENSP00000350162.2
SYCP2	ENST00000371001.6	c.2365-8T>A		splice_region_variant, intron_variant	Intron 23 of 43	1		ENSP00000360040.2
SYCP2	ENST00000446834.5	c.2365-8T>A		splice_region_variant, intron_variant	Intron 24 of 32	1		ENSP00000402456.1
SYCP2	ENST00000474749.1	n.-31T>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1411796 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 702270

African (AFR) AF: 0.0000327 AC: 1 AN: 30614

American (AMR) AF: 0.0000613 AC: 2 AN: 32648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24788

East Asian (EAS) AF: 0.00 AC: 0 AN: 38136

South Asian (SAS) AF: 0.00 AC: 0 AN: 78662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095866

Other (OTH) AF: 0.00 AC: 0 AN: 58424

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0080
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.030		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: rs193921008; hg19: chr20-58461897;