rs8009156

Positions:

• chr14-105643800-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641095.1(IGHG2):​c.481G>A​(p.Val161Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 779,382 control chromosomes in the GnomAD database, including 68,607 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10781 hom., cov: 34)
  • Exomes 𝑓: 0.41 (57826 hom.)
• Consequence: IGHG2 ENST00000641095.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

Genes affected

IGHG2 (HGNC:5526): (immunoglobulin heavy constant gamma 2 (G2m marker)) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Predicted to be involved in several processes, including activation of immune response; defense response to other organism; and phagocytosis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGHG2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHG2	unassigned_transcript_2471	c.478G>A	p.Val160Met	missense_variant	3/4
IGH		n.105643800C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHG2	ENST00000641095.1	c.481G>A	p.Val161Met	missense_variant	3/6			ENSP00000493129.1
IGHG2	ENST00000390545.3	c.481G>A	p.Val161Met	missense_variant	3/4	6		ENSP00000374987.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50615 AN: 151422 Hom.: 10779 Cov.: 34

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.394 AC: 97225 AN: 246622 Hom.: 22101 AF XY: 0.408 AC XY: 54659 AN XY: 133994

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.604

Gnomad EAS exome AF: 0.536

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.409 AC: 256701 AN: 627842 Hom.: 57826 Cov.: 0 AF XY: 0.415 AC XY: 142090 AN XY: 342024

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.334 AC: 50600 AN: 151540 Hom.: 10781 Cov.: 34 AF XY: 0.333 AC XY: 24633 AN XY: 74038

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.377

Alfa AF: 0.408 Hom.: 6073

Bravo AF: 0.314

Asia WGS AF: 0.437 AC: 1518 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8009156; hg19: chr14-106110137; COSMIC: COSV66640482;