rs1309743656

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020991.4(CSH2):c.346G>C(p.Val116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,457,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V116M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CSH2
NM_020991.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.116

Publications

0 publications found

Variant links:

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]

CSH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20709175).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSH2	NM_020991.4	MANE Select	c.346G>C	p.Val116Leu	missense	Exon 4 of 5	NP_066271.1	P0DML3-1
CSH2	NM_022644.3		c.346G>C	p.Val116Leu	missense	Exon 4 of 4	NP_072170.1	A6NIT4
CSH2	NM_022645.2		c.172-364G>C		intron	N/A	NP_072171.1	B1A4H9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSH2	ENST00000392886.7	TSL:1 MANE Select	c.346G>C	p.Val116Leu	missense	Exon 4 of 5	ENSP00000376623.2	P0DML3-1
CSH2	ENST00000613718.3	TSL:1	c.79G>C	p.Val27Leu	missense	Exon 3 of 4	ENSP00000478842.1	A0A087WUG6
CSH2	ENST00000336844.9	TSL:2	c.346G>C	p.Val116Leu	missense	Exon 4 of 4	ENSP00000338816.5	P0DML3-2

Frequencies

GnomAD3 genomes

AF:

0.00000708

AC:

AN:

141234

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad NFE

AF:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000427

AC:

AN:

234188

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1457568

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724820

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1110126

Other (OTH)

AF:

0.00

AC:

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000708

AC:

AN:

141234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37604

American (AMR)

AF:

0.00

AC:

AN:

13860

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4820

South Asian (SAS)

AF:

0.00

AC:

AN:

4020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

65038

Other (OTH)

AF:

0.00

AC:

AN:

1862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Benign

3.4

(source)

DANN

Benign

0.83

DEOGEN2

Uncertain

0.66

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.80

M_CAP

Benign

0.024

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.1

PhyloP100

0.12

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.32

Sift

Benign

0.28

Sift4G

Benign

0.19

Vest4

0.37

MutPred

0.54

Gain of phosphorylation at S111 (P = 0.2327)

MVP

0.46

ClinPred

0.18

GERP RS

1.7

Varity_R

0.063

gMVP

0.29

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over