rs1224346311

Variant names:

• chr2-24016208-C-G
• NM_001346880.2:c.275C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-24016208-C-G
• chr2-24016208-C-T

Variant summary

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

The NM_001346880.2(MFSD2B):​c.275C>G​(p.Ala92Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A92V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54

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.275C>G	p.Ala92Gly	missense_variant	Exon 3 of 14	ENST00000338315.6	NP_001333809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2B	ENST00000338315.6	c.275C>G	p.Ala92Gly	missense_variant	Exon 3 of 14	5	NM_001346880.2	ENSP00000342501.4
MFSD2B	ENST00000495018.1	n.330C>G		non_coding_transcript_exon_variant	Exon 3 of 6	1
MFSD2B	ENST00000669179.1	c.275C>G	p.Ala92Gly	missense_variant	Exon 3 of 15			ENSP00000499689.1
MFSD2B	ENST00000406420.7	c.275C>G	p.Ala92Gly	missense_variant	Exon 3 of 13	5		ENSP00000385527.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461602 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.61
Sift	Benign	0.040	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.56	.;P
Vest4		0.54
MutPred		0.76		Gain of disorder (P = 0.0611);Gain of disorder (P = 0.0611);
MVP		0.64
MPC		0.18
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.39
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr2-24239078;