Genetic Variant SYCP2:p.Arg1285His (chr20-59868547-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014258.4(SYCP2):c.3854G>A(p.Arg1285His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,602,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SYCP2
NM_014258.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.758

Publications

1 publications found

Variant links:

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]

SYCP2 Gene-Disease associations (from GenCC):

spermatogenic failure 1
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SYCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 35 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014258.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2	NM_014258.4	MANE Select	c.3854G>A	p.Arg1285His	missense	Exon 38 of 45	NP_055073.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYCP2	ENST00000357552.8	TSL:1 MANE Select	c.3854G>A	p.Arg1285His	missense	Exon 38 of 45	ENSP00000350162.2	Q9BX26
SYCP2	ENST00000371001.6	TSL:1	c.3854G>A	p.Arg1285His	missense	Exon 37 of 44	ENSP00000360040.2	Q9BX26
SYCP2	ENST00000412613.1	TSL:3	c.46+288G>A		intron	N/A	ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

151500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

241748

AF XY:

0.0000841

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000641

AC:

AN:

1451094

Hom.:

Cov.:

AF XY:

0.0000568

AC XY:

AN XY:

721632

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

32814

American (AMR)

AF:

0.0000236

AC:

AN:

42376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25798

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39336

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53022

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

1108686

Other (OTH)

AF:

0.0000835

AC:

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000231

AC:

AN:

151618

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.000748

AC:

AN:

41444

American (AMR)

AF:

0.0000659

AC:

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000947

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67694

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000590

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.59

M_CAP

Benign

0.0071

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.76

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.0

REVEL

Benign

0.015

Sift

Benign

0.055

Sift4G

Benign

0.18

Polyphen

0.055

Vest4

0.36

MVP

0.043

MPC

0.18

ClinPred

0.021

GERP RS

-0.15

PromoterAI

0.030

Neutral

(source)

Varity_R

0.027

gMVP

0.089

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 21

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over