1-39955401-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032793.5(MFSD2A):c.93+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,510,868 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (19 hom.)
• Consequence: MFSD2A NM_032793.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700

Genes affected

MFSD2A (HGNC:25897): (MFSD2 lysolipid transporter A, lysophospholipid) The protein encoded by this gene is a transmembrane protein and sodium-dependent lysophosphatidylcholine transporter. The encoded protein is involved in the establishment of the blood-brain barrier and is required for brain growth and function. Defects in this gene are a cause of a progressive microcephaly syndrome. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-39955401-C-A is Benign according to our data. Variant chr1-39955401-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1598360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00162 (246/152280) while in subpopulation EAS AF= 0.0157 (81/5160). AF 95% confidence interval is 0.0129. There are 1 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFSD2A	NM_032793.5	c.93+16C>A		intron_variant		ENST00000372811.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD2A	ENST00000372811.10	c.93+16C>A		intron_variant		1	NM_032793.5	P1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0159

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00467 AC: 631 AN: 135100 Hom.: 5 AF XY: 0.00363 AC XY: 265 AN XY: 73062

Gnomad AFR exome AF: 0.000107

Gnomad AMR exome AF: 0.0185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0186

Gnomad SAS exome AF: 0.00155

Gnomad FIN exome AF: 0.000950

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00122 AC: 1664 AN: 1358588 Hom.: 19 Cov.: 30 AF XY: 0.00117 AC XY: 781 AN XY: 667010

Gnomad4 AFR exome AF: 0.0000666

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0225

Gnomad4 SAS exome AF: 0.00172

Gnomad4 FIN exome AF: 0.00139

Gnomad4 NFE exome AF: 0.0000923

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00162 AC: 246 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74436

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0157

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000503 Hom.: 1

Bravo AF: 0.00277

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Microcephaly 15, primary, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
Dann	Benign	0.80

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: rs189000715; hg19: chr1-40421073; COSMIC: COSV65686438; COSMIC: COSV65686438;