Genetic Variant SDF2L1:p.Gly112Val (chr22-21643009-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022044.3(SDF2L1):c.335G>T(p.Gly112Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,562,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.50

Variant links:

Genes affected

SDF2L1 (HGNC:10676): (stromal cell derived factor 2 like 1) Enables misfolded protein binding activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

SDF2L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF2L1	NM_022044.3 link	c.335G>T	p.Gly112Val	missense_variant	Exon 2 of 3	ENST00000248958.5	NP_071327.2	Q9HCN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF2L1	ENST00000248958.5 link	c.335G>T	p.Gly112Val	missense_variant	Exon 2 of 3	1	NM_022044.3	ENSP00000248958.4		Q9HCN8
SDF2L1	ENST00000466935.1 link	n.318G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000180

AC:

AN:

166568

Hom.:

AF XY:

0.0000112

AC XY:

AN XY:

89216

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000218

GnomAD4 exome

AF:

0.0000135

AC:

AN:

1410186

Hom.:

Cov.:

AF XY:

0.00000861

AC XY:

AN XY:

696748

show subpopulations

Gnomad4 AFR exome

AF:

0.000558

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000105

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.0000647

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000232

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.335G>T (p.G112V) alteration is located in exon 2 (coding exon 2) of the SDF2L1 gene. This alteration results from a G to T substitution at nucleotide position 335, causing the glycine (G) at amino acid position 112 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.81

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

3.3

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.81

Sift

Benign

0.041

Sift4G

Benign

0.063

Polyphen

1.0

Vest4

0.88

MVP

1.0

MPC

1.6

ClinPred

0.88

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over