11-125954118-C-G

Variant names:

• chr11-125954118-C-G
• rs192608745
• NM_001365077.2:c.1818C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365077.2(VSIG10L2):​c.1818C>G​(p.Ser606Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000926 in 1,079,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S606S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: VSIG10L2 NM_001365077.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 0 publications found

Genes affected

VSIG10L2 (HGNC:27879): (V-set and immunoglobulin domain containing 10 like 2) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18143421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG10L2	NM_001365077.2	c.1818C>G	p.Ser606Arg	missense_variant	Exon 8 of 12	ENST00000686984.1	NP_001352006.1
VSIG10L2	NM_001391971.1	c.252C>G	p.Ser84Arg	missense_variant	Exon 2 of 4		NP_001378900.1
VSIG10L2	NM_001391972.1	c.221-1497C>G		intron_variant	Intron 1 of 2		NP_001378901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG10L2	ENST00000686984.1	c.1818C>G	p.Ser606Arg	missense_variant	Exon 8 of 12		NM_001365077.2	ENSP00000509422.1
VSIG10L2	ENST00000638511.1	n.283-1497C>G		intron_variant	Intron 1 of 2	1
VSIG10L2	ENST00000638636.2	c.1818C>G	p.Ser606Arg	missense_variant	Exon 8 of 10	5		ENSP00000491467.1
VSIG10L2	ENST00000640497.1	c.240C>G	p.Ser80Arg	missense_variant	Exon 2 of 4	3		ENSP00000491366.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1079964 Hom.: 0 Cov.: 31 AF XY: 0.00000196 AC XY: 1 AN XY: 509864

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22966

American (AMR) AF: 0.00 AC: 0 AN: 8418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14392

East Asian (EAS) AF: 0.0000377 AC: 1 AN: 26526

South Asian (SAS) AF: 0.00 AC: 0 AN: 19494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2914

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920038

Other (OTH) AF: 0.00 AC: 0 AN: 43680

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.79
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.39	T;T
MetaRNN	Benign	0.18	T;T
PhyloP100		0.91
GERP RS		1.3
Varity_R		0.082
gMVP		0.16
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs192608745; hg19: chr11-125824013;