17-63872726-G-C

Variant names:

• chr17-63872726-G-C
• NM_020991.4:c.307C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020991.4(CSH2):​c.307C>G​(p.Arg103Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000742 in 134,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000074 (0 hom., cov: 22)
• Consequence: CSH2 NM_020991.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

CSH2 (HGNC:2441): (chorionic somatomammotropin hormone 2) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones and plays an important role in growth control. The gene is located at the growth hormone locus on chromosome 17 along with four other related genes in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. Although the five genes share a remarkably high degree of sequence identity, they are expressed selectively in different tissues. Alternative splicing generates additional isoforms of each of the five growth hormones. This particular family member is expressed mainly in the placenta and utilizes multiple transcription initiation sites. Expression of the identical mature proteins for chorionic somatomammotropin hormones 1 and 2 is upregulated during development, while the ratio of 1 to 2 increases by term. Structural and expression differences provide avenues for developmental regulation and tissue specificity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSH2	NM_020991.4	c.307C>G	p.Arg103Gly	missense_variant	Exon 4 of 5	ENST00000392886.7	NP_066271.1
CSH2	NM_022644.3	c.307C>G	p.Arg103Gly	missense_variant	Exon 4 of 4		NP_072170.1
CSH2	NM_022645.2	c.172-403C>G		intron_variant	Intron 2 of 2		NP_072171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSH2	ENST00000392886.7	c.307C>G	p.Arg103Gly	missense_variant	Exon 4 of 5	1	NM_020991.4	ENSP00000376623.2

Frequencies

GnomAD3 genomes AF: 0.00000742 AC: 1 AN: 134744 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000742 AC: 1 AN: 134854 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 64696

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.80	D;.;D;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D;D;D;.
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Uncertain	2.8	M;M;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.1	D;D;D;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.011	D;D;D;.
Sift4G	Uncertain	0.034	D;D;D;D
Vest4		0.65
MutPred		0.69		Loss of phosphorylation at S105 (P = 0.0714);Loss of phosphorylation at S105 (P = 0.0714);.;.;
MVP		0.81
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.40
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61950086;