2-24017308-C-G

Variant names:

• chr2-24017308-C-G
• NM_001346880.2:c.494C>G

Variant summary

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

The NM_001346880.2(MFSD2B):​c.494C>G​(p.Ala165Gly) 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: MFSD2B NM_001346880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

Genes affected

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD2B	NM_001346880.2	c.494C>G	p.Ala165Gly	missense_variant	Exon 5 of 14	ENST00000338315.6	NP_001333809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2B	ENST00000338315.6	c.494C>G	p.Ala165Gly	missense_variant	Exon 5 of 14	5	NM_001346880.2	ENSP00000342501.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.494C>G (p.A165G) alteration is located in exon 5 (coding exon 5) of the MFSD2B gene. This alteration results from a C to G substitution at nucleotide position 494, causing the alanine (A) at amino acid position 165 to be replaced by a glycine (G). 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	0.31
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.57
Sift	Benign	0.066	T;T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.51	.;P
Vest4		0.80
MutPred		0.68		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.82
MPC		0.12
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.34
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-24240178;