2-24022514-C-G

Position:

• chr2-24022514-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346880.2(MFSD2B):​c.976C>G​(p.Leu326Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFSD2B NM_001346880.2 missense, splice_region
• Scores: Splicing: ADA: 0.1763
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.870

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFSD2B	NM_001346880.2	c.976C>G	p.Leu326Val	missense_variant, splice_region_variant	9/14	ENST00000338315.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD2B	ENST00000338315.6	c.976C>G	p.Leu326Val	missense_variant, splice_region_variant	9/14	5	NM_001346880.2	P2
MFSD2B	ENST00000469562.1	n.412C>G		splice_region_variant, non_coding_transcript_exon_variant	4/8	1
MFSD2B	ENST00000669179.1	c.1060C>G	p.Leu354Val	missense_variant, splice_region_variant	10/15			A2
MFSD2B	ENST00000406420.7	c.976C>G	p.Leu326Val	missense_variant, splice_region_variant	9/13	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 20, 2024

The c.976C>G (p.L326V) alteration is located in exon 9 (coding exon 9) of the MFSD2B gene. This alteration results from a C to G substitution at nucleotide position 976, causing the leucine (L) at amino acid position 326 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	0.028	D
MutationAssessor	Benign	2.0	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.94	.;P
Vest4		0.41
MutPred		0.41		Gain of catalytic residue at L326 (P = 0.0036);Gain of catalytic residue at L326 (P = 0.0036);
MVP		0.75
MPC		0.34
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.26
SpliceAI score (max)		0.17		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: chr2-24245384;