6-10912760-G-A

Variant names:

• chr6-10912760-G-A
• rs199768634
• NM_001040274.3:c.1006G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001040274.3(SYCP2L):​c.1006G>A​(p.Ala336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,244 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780

Genes affected

SYCP2L (HGNC:21537): (synaptonemal complex protein 2 like) Predicted to be involved in meiotic nuclear division. Predicted to act upstream of or within negative regulation of cell death. Located in condensed chromosome, centromeric region and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272162 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021714687).
• BP6: Variant 6-10912760-G-A is Benign according to our data. Variant chr6-10912760-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2276474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3	c.1006G>A	p.Ala336Thr	missense_variant	Exon 13 of 30	ENST00000283141.11	NP_001035364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2L	ENST00000283141.11	c.1006G>A	p.Ala336Thr	missense_variant	Exon 13 of 30	1	NM_001040274.3	ENSP00000283141.6
ENSG00000272162	ENST00000480294.1	n.*968G>A		non_coding_transcript_exon_variant	Exon 15 of 19	2		ENSP00000417929.1
ENSG00000272162	ENST00000480294.1	n.*968G>A		3_prime_UTR_variant	Exon 15 of 19	2		ENSP00000417929.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000116 AC: 29 AN: 249080 Hom.: 0 AF XY: 0.000155 AC XY: 21 AN XY: 135124

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000179 AC: 261 AN: 1460978 Hom.: 2 Cov.: 30 AF XY: 0.000187 AC XY: 136 AN XY: 726824

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74444

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.000140

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000269 AC: 1

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000993 AC: 12

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 27, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.87
DEOGEN2	Benign	0.00094	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.022	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.14	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.46	N;.
REVEL	Benign	0.035
Sift	Benign	0.54	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0080	B;.
Vest4		0.13
MVP		0.088
MPC		0.12
ClinPred		0.011	T
GERP RS		-2.4
Varity_R		0.033
gMVP		0.087

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

LitVar

Other links and lift over

dbSNP: rs199768634; hg19: chr6-10912993;