6-37028997-C-G

Variant summary

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

The NM_173558.4(FGD2):c.*834C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,584 control chromosomes in the GnomAD database, including 24,331 homozygotes. 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: 𝑓 0.56 (24328 hom., cov: 28)
  • Exomes 𝑓: 0.50 (3 hom.)
• Consequence: FGD2 NM_173558.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771

Genes affected

FGD2 (HGNC:3664): (FYVE, RhoGEF and PH domain containing 2) The protein encoded by this gene belongs to a family of guanine nucleotide exchange factors (GEFs) which control cytoskeleton-dependent membrane rearrangements by activating the cell division cycle 42 (CDC42) protein. This gene is expressed in B lymphocytes, macrophages, and dendritic cells. The encoded protein may play a role in leukocyte signaling and vesicle trafficking in antigen-presenting cells in the immune system. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD2	NM_173558.4	c.*834C>G		3_prime_UTR_variant	16/16	ENST00000274963.13
FGD2	XM_047418333.1	c.*834C>G		3_prime_UTR_variant	13/13
FGD2	XM_047418334.1	c.*834C>G		3_prime_UTR_variant	11/11
FGD2	XM_047418335.1	c.*834C>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD2	ENST00000274963.13	c.*834C>G		3_prime_UTR_variant	16/16	1	NM_173558.4	P1
FGD2	ENST00000487920.1	n.2545C>G		non_coding_transcript_exon_variant	3/3	2
FGD2	ENST00000494343.5	n.2859C>G		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84726 AN: 151450 Hom.: 24305 Cov.: 28

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.500 AC: 8 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.560 AC: 84803 AN: 151568 Hom.: 24328 Cov.: 28 AF XY: 0.565 AC XY: 41786 AN XY: 74018

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.555

Alfa AF: 0.523 Hom.: 2689

Bravo AF: 0.573

Asia WGS AF: 0.684 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.75
Dann	Benign	0.39

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: rs708017; hg19: chr6-36996773;