rs61750906

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_017826.3(SOHLH2):c.1205G>A(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,613,976 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.019 ( 322 hom. )

Consequence

SOHLH2
NM_017826.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.19

Publications

7 publications found

Variant links:

Genes affected

SOHLH2 (HGNC:26026): (spermatogenesis and oogenesis specific basic helix-loop-helix 2) This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 13. The proteins encoded by this gene and another testis-specific transcription factor, SOHLH1, can form heterodimers, in addition to homodimers. There is a read-through locus (GeneID: 100526761) that shares sequence identity with this gene and the upstream CCDC169 (GeneID: 728591). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

SOHLH2 links:

CCDC169-SOHLH2 (HGNC:38866): (CCDC169-SOHLH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C13orf38 (chromosome 13 open reading frame 38) and SOHLH2 (spermatogenesis and oogenesis specific basic helix-loop-helix 2) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

CCDC169-SOHLH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019699037).

BP6

Variant 13-36170583-C-T is Benign according to our data. Variant chr13-36170583-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3038235.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0146 (2218/152108) while in subpopulation NFE AF = 0.021 (1428/67996). AF 95% confidence interval is 0.0201. There are 26 homozygotes in GnomAd4. There are 1099 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017826.3. 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
	SOHLH2	NM_017826.3	MANE Select	c.1205G>A	p.Arg402Gln	missense	Exon 10 of 11	NP_060296.2	Q9NX45-1
	CCDC169-SOHLH2	NM_001198910.2		c.1436G>A	p.Arg479Gln	missense	Exon 15 of 16	NP_001185839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH2	ENST00000379881.8	TSL:1 MANE Select	c.1205G>A	p.Arg402Gln	missense	Exon 10 of 11	ENSP00000369210.3	Q9NX45-1
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.1436G>A	p.Arg479Gln	missense	Exon 15 of 16	ENSP00000421868.1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2220

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0143

AC:

3599

AN:

251308

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0377

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0187

AC:

27327

AN:

1461868

Hom.:

322

Cov.:

AF XY:

0.0184

AC XY:

13357

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00320

AC:

107

AN:

33480

American (AMR)

AF:

0.00639

AC:

286

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00765

AC:

200

AN:

26136

East Asian (EAS)

AF:

0.00111

AC:

AN:

39700

South Asian (SAS)

AF:

0.00528

AC:

455

AN:

86254

European-Finnish (FIN)

AF:

0.0378

AC:

2018

AN:

53418

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0209

AC:

23277

AN:

1111994

Other (OTH)

AF:

0.0153

AC:

925

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

874

1748

2622

3496

4370

<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

AF:

0.0146

AC:

2218

AN:

152108

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1099

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00359

AC:

149

AN:

41484

American (AMR)

AF:

0.0114

AC:

175

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.00374

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0370

AC:

391

AN:

10580

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0210

AC:

1428

AN:

67996

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0179

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0193

AC:

166

ExAC

AF:

0.0138

AC:

1674

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0179

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CCDC169-SOHLH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.067

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

PhyloP100

2.2

PrimateAI

Benign

0.28

PROVEAN

Benign

1.0

REVEL

Benign

0.047

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.026

MPC

0.24

ClinPred

0.0075

GERP RS

2.7

Varity_R

0.024

gMVP

0.044

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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