2-200469989-A-G

Position:

• chr2-200469989-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001100423.2(SPATS2L):​c.1033A>G​(p.Lys345Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATS2L NM_001100423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

Genes affected

SPATS2L (HGNC:24574): (spermatogenesis associated serine rich 2 like) Enables RNA binding activity. Located in cytosol; nucleolus; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATS2L	NM_001100423.2	c.1033A>G	p.Lys345Glu	missense_variant	11/13	ENST00000409140.8	NP_001093893.1
LOC101927741	XR_007088047.1	n.569+6114T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8	c.1033A>G	p.Lys345Glu	missense_variant	11/13	2	NM_001100423.2	ENSP00000386730	P1
	ENST00000655656.1	n.566+6114T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jul 25, 2023

The c.1033A>G (p.K345E) alteration is located in exon 11 (coding exon 9) of the SPATS2L gene. This alteration results from a A to G substitution at nucleotide position 1033, causing the lysine (K) at amino acid position 345 to be replaced by a glutamic acid (E). 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	0.58
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T;T;T;.;T;.;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;.;.;D;.;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.6	M;M;M;.;M;.;M;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;.;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.013	D;D;D;D;D;D;D;.;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D;D;D;.
Polyphen		1.0	D;D;D;.;D;D;D;.;.
Vest4		0.85
MutPred		0.72		Loss of ubiquitination at K345 (P = 0.0148);Loss of ubiquitination at K345 (P = 0.0148);Loss of ubiquitination at K345 (P = 0.0148);.;Loss of ubiquitination at K345 (P = 0.0148);.;Loss of ubiquitination at K345 (P = 0.0148);.;.;
MVP		0.23
MPC		1.1
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.51
gMVP		0.69

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: chr2-201334712;