11-62691130-T-G

Variant names:

• chr11-62691130-T-G
• NM_001122955.4:c.1017A>C
• BSCL2 p.Arg339Arg

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130702.2(BSCL2):​c.683A>C​(p.Glu228Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E228G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BSCL2 NM_001130702.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

Genes affected

BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]

HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060326844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130702.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	NM_001122955.4	MANE Select	c.1017A>C	p.Arg339Arg	synonymous	Exon 8 of 11	NP_001116427.1	Q96G97-4
	BSCL2	NM_001130702.2		c.683A>C	p.Glu228Ala	missense	Exon 7 of 10	NP_001124174.2	Q96G97-3
	BSCL2	NM_001386027.1		c.1017A>C	p.Arg339Arg	synonymous	Exon 9 of 12	NP_001372956.1	J3KQ12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	ENST00000360796.10	TSL:1 MANE Select	c.1017A>C	p.Arg339Arg	synonymous	Exon 8 of 11	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.1017A>C	p.Arg339Arg	synonymous	Exon 9 of 12	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.825A>C	p.Arg275Arg	synonymous	Exon 8 of 11	ENSP00000384080.3	Q96G97-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	2.2
DANN	Benign	0.75
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.74	T
PhyloP100		-1.5
PROVEAN	Benign	1.2	N
REVEL	Benign	0.10
Sift	Benign	0.45	T
Sift4G	Benign	0.22	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-62458602;