14-105644577-G-T

Variant names:

• chr14-105644577-G-T
• rs11627594
• ENST00000641095.1:c.214C>A

Variant summary

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

The ENST00000641095.1(IGHG2):​c.214C>A​(p.Pro72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 774,208 control chromosomes in the GnomAD database, including 66,816 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 (10321 hom., cov: 33)
  • Exomes 𝑓: 0.41 (56495 hom.)
• Consequence: IGHG2 ENST00000641095.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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]

IGH (HGNC:5477):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHG2	unassigned_transcript_2471	c.211C>A	p.Pro71Thr	missense_variant	Exon 1 of 4
IGH		n.105644577G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHG2	ENST00000641095.1	c.214C>A	p.Pro72Thr	missense_variant	Exon 1 of 6			ENSP00000493129.1
IGHG2	ENST00000390545.3	c.214C>A	p.Pro72Thr	missense_variant	Exon 1 of 4	6		ENSP00000374987.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 49734 AN: 148816 Hom.: 10319 Cov.: 33

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.395 AC: 97037 AN: 245892 Hom.: 22172 AF XY: 0.408 AC XY: 54535 AN XY: 133544

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.536

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.407 AC: 254466 AN: 625270 Hom.: 56495 Cov.: 0 AF XY: 0.413 AC XY: 140865 AN XY: 340702

Gnomad4 AFR exome AF: 0.0790

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.334 AC: 49721 AN: 148938 Hom.: 10321 Cov.: 33 AF XY: 0.332 AC XY: 24153 AN XY: 72666

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.374

Alfa AF: 0.401 Hom.: 3841

Bravo AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.93

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: rs11627594; hg19: chr14-106110914; COSMIC: COSV66640485;