2-20678646-T-C

Position:

• chr2-20678646-T-C

Variant summary

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

The NM_182828.4(GDF7):​c.*7221T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,248 control chromosomes in the GnomAD database, including 8,294 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 0.30 (8293 hom., cov: 33)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: GDF7 NM_182828.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922

Genes affected

GDF7 (HGNC:4222): (growth differentiation factor 7) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein may play a role in the differentiation of tendon cells and spinal cord interneurons. A mutation in this gene may be associated with increased risk for Barrett's esophagus and esophageal adenocarcinoma. [provided by RefSeq, Sep 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF7	NM_182828.4	c.*7221T>C		3_prime_UTR_variant	2/2	ENST00000272224.5
GDF7	XM_047443522.1	c.*7221T>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF7	ENST00000272224.5	c.*7221T>C		3_prime_UTR_variant	2/2	1	NM_182828.4	P1
	ENST00000602445.1	n.287A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46291 AN: 152124 Hom.: 8285 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.304 AC: 46298 AN: 152242 Hom.: 8293 Cov.: 33 AF XY: 0.307 AC XY: 22846 AN XY: 74446

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.366

Alfa AF: 0.372 Hom.: 15611

Bravo AF: 0.290

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.67
DANN	Benign	0.53

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: rs3072; hg19: chr2-20878406;