chr2-24017484-C-A

Variant names:

• chr2-24017484-C-A
• rs1411009740
• NM_001346880.2:c.577C>A

Variant summary

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

The NM_001346880.2(MFSD2B):​c.577C>A​(p.Leu193Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.114

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 rank	MANE	Protein	UniProt
MFSD2B	NM_001346880.2	c.577C>A	p.Leu193Met	missense_variant	Exon 6 of 14	ENST00000338315.6	NP_001333809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2B	ENST00000338315.6	c.577C>A	p.Leu193Met	missense_variant	Exon 6 of 14	5	NM_001346880.2	ENSP00000342501.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447652 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000233

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.577C>A (p.L193M) alteration is located in exon 6 (coding exon 6) of the MFSD2B gene. This alteration results from a C to A substitution at nucleotide position 577, causing the leucine (L) at amino acid position 193 to be replaced by a methionine (M). 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	0.26
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.0027
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.59
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.99	.;D
Vest4		0.54
MutPred		0.67		Gain of disorder (P = 0.0345);Gain of disorder (P = 0.0345);
MVP		0.54
MPC		0.38
ClinPred		0.85	D
GERP RS		2.4
Varity_R		0.32
gMVP		0.39

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

Other links and lift over

dbSNP: rs1411009740; hg19: chr2-24240354;