2-24017528-C-G

Variant names:

• chr2-24017528-C-G
• rs769192324
• NM_001346880.2:c.621C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346880.2(MFSD2B):​c.621C>G​(p.His207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000049 in 1,427,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1504974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD2B	NM_001346880.2	c.621C>G	p.His207Gln	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.621C>G	p.His207Gln	missense_variant	Exon 6 of 14	5	NM_001346880.2	ENSP00000342501.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000261 AC: 5 AN: 191396 Hom.: 0 AF XY: 0.0000291 AC XY: 3 AN XY: 103266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000490 AC: 7 AN: 1427192 Hom.: 0 Cov.: 32 AF XY: 0.00000566 AC XY: 4 AN XY: 706726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000101

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: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.9
DANN	Benign	0.83
DEOGEN2	Uncertain	0.47	.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.68	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.025	D;D
Sift4G	Benign	0.070	T;T
Polyphen		0.037	.;B
Vest4		0.51
MutPred		0.46		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.26
MPC		0.30
ClinPred		0.051	T
GERP RS		1.4
Varity_R		0.18
gMVP		0.43

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: rs769192324; hg19: chr2-24240398;