22-22697977-T-G

Variant names:

• chr22-22697977-T-G
• rs1312
• ENST00000390306.2:c.27T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000390306.2(IGLV2-23):​c.27T>G​(p.Thr9Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 625,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: IGLV2-23 ENST00000390306.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 6 publications found

Genes affected

IGLV2-23 (HGNC:5890): (immunoglobulin lambda variable 2-23) Predicted to be involved in immune response. Predicted to be located in extracellular region and plasma membrane. Predicted to be part of immunoglobulin complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGL (HGNC:5853):

LL22NC03-102D1.18 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390306.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLV2-23	ENST00000390306.2	TSL:6	c.27T>G	p.Thr9Thr	synonymous	Exon 1 of 2	ENSP00000374841.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000843 AC: 2 AN: 237308 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000320 AC: 2 AN: 625090 Hom.: 0 Cov.: 0 AF XY: 0.00000587 AC XY: 2 AN XY: 340500

African (AFR) AF: 0.00 AC: 0 AN: 17584

American (AMR) AF: 0.00 AC: 0 AN: 42874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20850

East Asian (EAS) AF: 0.00 AC: 0 AN: 35988

South Asian (SAS) AF: 0.0000287 AC: 2 AN: 69588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 348314

Other (OTH) AF: 0.00 AC: 0 AN: 32958

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-2.9

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

Other links and lift over

dbSNP: rs1312; hg19: chr22-23040462;