2-20678393-T-C

Position:

• chr2-20678393-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.*6968T>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 0.3 in 152,270 control chromosomes in the GnomAD database, including 8,046 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 (8046 hom., cov: 34)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GDF7 NM_182828.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF7	NM_182828.4	c.*6968T>C		3_prime_UTR_variant	2/2	ENST00000272224.5	NP_878248.2
GDF7	XM_047443522.1	c.*6968T>C		3_prime_UTR_variant	2/2		XP_047299478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF7	ENST00000272224.5	c.*6968T>C		3_prime_UTR_variant	2/2	1	NM_182828.4	ENSP00000272224	P1
	ENST00000602445.1	n.540A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45629 AN: 152150 Hom.: 8039 Cov.: 34

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.300 AC: 45633 AN: 152266 Hom.: 8046 Cov.: 34 AF XY: 0.303 AC XY: 22549 AN XY: 74444

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.357

Alfa AF: 0.350 Hom.: 2263

Bravo AF: 0.286

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.80

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: rs9306895; hg19: chr2-20878153;