Genetic Variant XM_024450773.2:c.4810-126068C>T (chr17-46922988-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The XM_024450773.2(LRRC37A2):c.4810-126068C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 616,552 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 33 hom. )

Consequence

LRRC37A2
XM_024450773.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00

Publications

2 publications found

Variant links:

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

GOSR2-DT links:

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GOSR2 Gene-Disease associations (from GenCC):

progressive myoclonus epilepsy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
progressive myoclonic epilepsy type 6
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
muscular dystrophy, congenital, with or without seizures
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GOSR2 links:

ENSG00000262633 (HGNC:):

ENSG00000262633 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-46922988-C-T is Benign according to our data. Variant chr17-46922988-C-T is described in ClinVar as Benign. ClinVar VariationId is 1230145.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000640051.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GOSR2	NM_004287.5	MANE Select	c.-205C>T	upstream_gene	N/A	NP_004278.2
GOSR2	NM_001321133.2		c.-205C>T	upstream_gene	N/A	NP_001308062.1	I3NI02
GOSR2	NM_054022.4		c.-205C>T	upstream_gene	N/A	NP_473363.1	O14653-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GOSR2-DT	ENST00000572349.2	TSL:3	n.115G>A	non_coding_transcript_exon	Exon 1 of 3
GOSR2-DT	ENST00000715847.1		n.92G>A	non_coding_transcript_exon	Exon 1 of 2
GOSR2-DT	ENST00000750339.1		n.139G>A	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2423

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00860

GnomAD4 exome

AF:

0.00213

AC:

990

AN:

464202

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

446

AN XY:

246330

show subpopulations

African (AFR)

AF:

0.0566

AC:

739

AN:

13064

American (AMR)

AF:

0.00354

AC:

AN:

22304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14372

East Asian (EAS)

AF:

0.00

AC:

AN:

31312

South Asian (SAS)

AF:

0.000228

AC:

AN:

48268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29748

Middle Eastern (MID)

AF:

0.000989

AC:

AN:

2022

European-Non Finnish (NFE)

AF:

0.000123

AC:

AN:

276426

Other (OTH)

AF:

0.00468

AC:

125

AN:

26686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0159

AC:

2426

AN:

152350

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1137

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0556

AC:

2312

AN:

41576

American (AMR)

AF:

0.00529

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68036

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

115

230

345

460

575

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:

0.00893

Hom.:

Bravo

AF:

0.0186

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

(source)

DANN

Benign

0.86

PhyloP100

-1.0

PromoterAI

-0.014

Neutral

(source)

Splicing

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