rs116889214

Variant names:

• chr17-63872128-A-G
• rs116889214
• NM_020991.4:c.652T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_020991.4(CSH2):​c.652T>C​(p.Ter218Glnext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00425 in 1,614,102 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0044 (67 hom.)
• Consequence: CSH2 NM_020991.4 stop_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.01
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• PM4: Stoplost variant in NM_020991.4 Downstream stopcodon found after 0 codons.
• BP6: Variant 17-63872128-A-G is Benign according to our data. Variant chr17-63872128-A-G is described in ClinVar as Benign. ClinVar VariationId is 717494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020991.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH2	NM_020991.4	MANE Select	c.652T>C	p.Ter218Glnext*?	stop_lost	Exon 5 of 5	NP_066271.1	P0DML3-1
	CSH2	NM_022645.2		c.367T>C	p.Ter123Glnext*?	stop_lost	Exon 3 of 3	NP_072171.1	B1A4H9
	CSH2	NM_022644.3		c.*401T>C		3_prime_UTR	Exon 4 of 4	NP_072170.1	A6NIT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH2	ENST00000392886.7	TSL:1 MANE Select	c.652T>C	p.Ter218Glnext*?	stop_lost	Exon 5 of 5	ENSP00000376623.2	P0DML3-1
	CSH2	ENST00000613718.3	TSL:1	c.385T>C	p.Ter129Glnext*?	stop_lost	Exon 4 of 4	ENSP00000478842.1	A0A087WUG6
	CSH2	ENST00000560142.5	TSL:5	c.481T>C	p.Ter161Glnext*?	stop_lost	Exon 5 of 5	ENSP00000453452.1	H0YM39

Frequencies

GnomAD3 genomes AF: 0.00301 AC: 458 AN: 152166 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00490

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00358 AC: 901 AN: 251390 AF XY: 0.00339

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00721

Gnomad NFE exome AF: 0.00535

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00438 AC: 6401 AN: 1461818 Hom.: 67 Cov.: 31 AF XY: 0.00419 AC XY: 3047 AN XY: 727214

African (AFR) AF: 0.000568 AC: 19 AN: 33478

American (AMR) AF: 0.00181 AC: 81 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00181 AC: 156 AN: 86258

European-Finnish (FIN) AF: 0.00721 AC: 385 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00497 AC: 5523 AN: 1111946

Other (OTH) AF: 0.00384 AC: 232 AN: 60392

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152284 Hom.: 3 Cov.: 29 AF XY: 0.00313 AC XY: 233 AN XY: 74464

African (AFR) AF: 0.000673 AC: 28 AN: 41578

American (AMR) AF: 0.00170 AC: 26 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00490 AC: 333 AN: 67994

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00397 Hom.: 3

Bravo AF: 0.00272

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00368 AC: 447

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00356

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.67
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		6.0
Vest4		0.30
GERP RS		4.0
Mutation Taster		=110/90	polymorphism

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: rs116889214; hg19: chr17-61949488;