2-24017358-G-T

Position:

• chr2-24017358-G-T

Variant summary

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

The NM_001346880.2(MFSD2B):​c.544G>T​(p.Ala182Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

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.544G>T	p.Ala182Ser	missense_variant	5/14	ENST00000338315.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD2B	ENST00000338315.6	c.544G>T	p.Ala182Ser	missense_variant	5/14	5	NM_001346880.2	P2
MFSD2B	ENST00000495018.1	n.527-100G>T		intron_variant, non_coding_transcript_variant		1
MFSD2B	ENST00000669179.1	c.544G>T	p.Ala182Ser	missense_variant	5/15			A2
MFSD2B	ENST00000406420.7	c.544G>T	p.Ala182Ser	missense_variant	5/13	5		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451618 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721300

Gnomad4 AFR exome AF: 0.00

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: 0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.544G>T (p.A182S) alteration is located in exon 5 (coding exon 5) of the MFSD2B gene. This alteration results from a G to T substitution at nucleotide position 544, causing the alanine (A) at amino acid position 182 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.022
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	-0.0087	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.99	.;D
Vest4		0.60
MutPred		0.68		Gain of disorder (P = 0.0293);Gain of disorder (P = 0.0293);
MVP		0.76
MPC		0.36
ClinPred		0.96	D
GERP RS		2.5
Varity_R		0.24
gMVP		0.48

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: rs895534026; hg19: chr2-24240228;