rs2006123

Variant names:

• chr17-63881309-G-T
• rs2006123
• NM_002059.5:c.171+50C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002059.5(GH2):​c.171+50C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,074 control chromosomes in the GnomAD database, including 76,592 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 0.38 (14431 hom., cov: 32)
  • Exomes 𝑓: 0.28 (62161 hom.)
• Consequence: GH2 NM_002059.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 8 publications found

Genes affected

GH2 (HGNC:4262): (growth hormone 2) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. As in the case of its pituitary counterpart, growth hormone 1, the predominant isoform of this particular family member shows similar somatogenic activity, with reduced lactogenic activity. Mutations in this gene lead to placental growth hormone/lactogen deficiency. [provided by RefSeq, Jul 2008]

ENSG00000303037 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH2	NM_002059.5	c.171+50C>A		intron_variant	Intron 2 of 4	ENST00000423893.7	NP_002050.1
GH2	NM_022557.4	c.171+50C>A		intron_variant	Intron 2 of 3		NP_072051.1
GH2	NM_022558.4	c.171+50C>A		intron_variant	Intron 2 of 4		NP_072052.1
GH2	NM_022556.4	c.171+50C>A		intron_variant	Intron 2 of 4		NP_072050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH2	ENST00000423893.7	c.171+50C>A		intron_variant	Intron 2 of 4	1	NM_002059.5	ENSP00000409294.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57601 AN: 151794 Hom.: 14381 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.345

GnomAD2 exomes AF: 0.265 AC: 66475 AN: 250732 AF XY: 0.258

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.0464

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.275 AC: 401677 AN: 1460162 Hom.: 62161 Cov.: 33 AF XY: 0.272 AC XY: 197361 AN XY: 726542

African (AFR) AF: 0.726 AC: 24288 AN: 33460

American (AMR) AF: 0.225 AC: 10083 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 7208 AN: 26120

East Asian (EAS) AF: 0.0499 AC: 1980 AN: 39696

South Asian (SAS) AF: 0.181 AC: 15620 AN: 86212

European-Finnish (FIN) AF: 0.221 AC: 11820 AN: 53410

Middle Eastern (MID) AF: 0.319 AC: 1840 AN: 5768

European-Non Finnish (NFE) AF: 0.281 AC: 312330 AN: 1110418

Other (OTH) AF: 0.274 AC: 16508 AN: 60358

GnomAD4 genome AF: 0.380 AC: 57693 AN: 151912 Hom.: 14431 Cov.: 32 AF XY: 0.370 AC XY: 27438 AN XY: 74246

African (AFR) AF: 0.712 AC: 29460 AN: 41398

American (AMR) AF: 0.249 AC: 3807 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3472

East Asian (EAS) AF: 0.0556 AC: 288 AN: 5182

South Asian (SAS) AF: 0.172 AC: 828 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10556

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19128 AN: 67906

Other (OTH) AF: 0.341 AC: 719 AN: 2106

Alfa AF: 0.320 Hom.: 3024

Bravo AF: 0.398

Asia WGS AF: 0.161 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.070
DANN	Benign	0.83
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs2006123; hg19: chr17-61958669; COSMIC: COSV60426496; COSMIC: COSV60426496;