14-105644563-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000641095.1(IGHG2):c.228C>G(p.Phe76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 774,688 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (15 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (73 hom.)
• Consequence: IGHG2 ENST00000641095.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0950

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-105644563-G-C is Benign according to our data. Variant chr14-105644563-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHG2	ENST00000641095.1	c.228C>G	p.Phe76Leu	missense_variant	1/6			P5
IGHG2	ENST00000390545.3	c.228C>G	p.Phe76Leu	missense_variant	1/4			A2

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 850 AN: 150084 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00727

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00944

Gnomad FIN AF: 0.00266

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00887

Gnomad OTH AF: 0.00388

GnomAD3 exomes AF: 0.00127 AC: 312 AN: 245704 Hom.: 7 AF XY: 0.00131 AC XY: 175 AN XY: 133496

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.000899

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00190

Gnomad FIN exome AF: 0.000419

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00655 AC: 4091 AN: 624484 Hom.: 73 Cov.: 0 AF XY: 0.00673 AC XY: 2288 AN XY: 340158

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00243

Gnomad4 ASJ exome AF: 0.00540

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.00946

Gnomad4 FIN exome AF: 0.00266

Gnomad4 NFE exome AF: 0.00811

Gnomad4 OTH exome AF: 0.00634

GnomAD4 genome AF: 0.00565 AC: 849 AN: 150204 Hom.: 15 Cov.: 33 AF XY: 0.00508 AC XY: 373 AN XY: 73448

Gnomad4 AFR AF: 0.00191

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00727

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00945

Gnomad4 FIN AF: 0.00266

Gnomad4 NFE AF: 0.00888

Gnomad4 OTH AF: 0.00384

Alfa AF: 0.00194 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RP11-731F5.1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_noAF	Benign	-0.93
Cadd	Benign	4.0
Dann	Benign	0.77

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: rs200481020; hg19: chr14-106110900;