6-109442864-C-G

Position:

• chr6-109442864-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003080.3(SMPD2):​c.604C>G​(p.Leu202Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMPD2 NM_003080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182

Genes affected

SMPD2 (HGNC:11121): (sphingomyelin phosphodiesterase 2) This gene encodes a protein which was initially identified as a sphingomyelinase based on sequence similarity between bacterial sphingomyelinases and a yeast protein. Subsequent studies showed that its biological function is less likely to be as a sphingomyelinase and instead as a lysophospholipase. [provided by RefSeq, Oct 2009]

SMPD2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0597167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD2	NM_003080.3	c.604C>G	p.Leu202Val	missense_variant	7/10	ENST00000258052.8	NP_003071.2
SMPD2	XM_011536079.2	c.289C>G	p.Leu97Val	missense_variant	5/8		XP_011534381.1
SMPD2	XR_942566.3	n.1002C>G		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD2	ENST00000258052.8	c.604C>G	p.Leu202Val	missense_variant	7/10	1	NM_003080.3	ENSP00000258052.3
SMPD2	ENST00000458487.1	c.292C>G	p.Leu98Val	missense_variant	1/4	2		ENSP00000399731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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, 2024

The c.604C>G (p.L202V) alteration is located in exon 7 (coding exon 7) of the SMPD2 gene. This alteration results from a C to G substitution at nucleotide position 604, causing the leucine (L) at amino acid position 202 to be replaced by a valine (V). 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	Benign	0.068
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.52	T
Polyphen		0.032	B
Vest4		0.18
MutPred		0.37		Gain of phosphorylation at Y201 (P = 0.1975);
MVP		0.69
MPC		0.081
ClinPred		0.056	T
GERP RS		4.1
Varity_R		0.10
gMVP		0.40

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: chr6-109764067;