14-105644577-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• recurrent infections associated with rare immunoglobulin isotypes deficiency

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641095.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG2	ENST00000641095.1		c.214C>A	p.Pro72Thr	missense	Exon 1 of 6	ENSP00000493129.1
	IGHG2	ENST00000390545.3	TSL:6	c.214C>A	p.Pro72Thr	missense	Exon 1 of 4	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

GnomAD2 exomes AF: 0.395 AC: 97037 AN: 245892 AF XY: 0.408

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 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

African (AFR) AF: 0.0790 AC: 1391 AN: 17618

American (AMR) AF: 0.222 AC: 9687 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 12341 AN: 20902

East Asian (EAS) AF: 0.266 AC: 9575 AN: 36038

South Asian (SAS) AF: 0.376 AC: 26175 AN: 69528

European-Finnish (FIN) AF: 0.415 AC: 22023 AN: 53036

Middle Eastern (MID) AF: 0.531 AC: 1335 AN: 2514

European-Non Finnish (NFE) AF: 0.452 AC: 157925 AN: 349116

Other (OTH) AF: 0.427 AC: 14014 AN: 32846

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

African (AFR) AF: 0.0843 AC: 3400 AN: 40352

American (AMR) AF: 0.288 AC: 4320 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2049 AN: 3392

East Asian (EAS) AF: 0.485 AC: 2424 AN: 5000

South Asian (SAS) AF: 0.380 AC: 1783 AN: 4688

European-Finnish (FIN) AF: 0.414 AC: 4297 AN: 10382

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.450 AC: 30103 AN: 66918

Other (OTH) AF: 0.374 AC: 762 AN: 2038

Alfa AF: 0.401 Hom.: 3841

Bravo AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		-0.16

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