rs2059397

Variant names:

• chr1-217544790-C-G
• rs2059397
• NM_018040.5:c.1099-29901G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018040.5(GPATCH2):​c.1099-29901G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 152,298 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.018 (41 hom., cov: 33)
• Consequence: GPATCH2 NM_018040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 6 publications found

Genes affected

GPATCH2 (HGNC:25499): (G-patch domain containing 2) The gene encodes a nuclear factor that may play a role in spermatogenesis and in tumor growth during breast cancer. The encoded protein contains a G-patch domain with an RNA binding motif. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.018 (2744/152298) while in subpopulation SAS AF = 0.0351 (169/4820). AF 95% confidence interval is 0.0307. There are 41 homozygotes in GnomAd4. There are 1424 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018040.5. 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
	GPATCH2	NM_018040.5	MANE Select	c.1099-29901G>C		intron	N/A	NP_060510.1	Q9NW75-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPATCH2	ENST00000366935.8	TSL:2 MANE Select	c.1099-29901G>C		intron	N/A	ENSP00000355902.3	Q9NW75-1
	GPATCH2	ENST00000885578.1		c.1090-29901G>C		intron	N/A	ENSP00000555637.1
	GPATCH2	ENST00000911527.1		c.1099-29901G>C		intron	N/A	ENSP00000581586.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2744 AN: 152180 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0180 AC: 2744 AN: 152298 Hom.: 41 Cov.: 33 AF XY: 0.0191 AC XY: 1424 AN XY: 74468

African (AFR) AF: 0.00298 AC: 124 AN: 41570

American (AMR) AF: 0.0125 AC: 192 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0351 AC: 169 AN: 4820

European-Finnish (FIN) AF: 0.0426 AC: 452 AN: 10612

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1481 AN: 68026

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0221 Hom.: 5

Bravo AF: 0.0146

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.71
PhyloP100		-0.33
Mutation Taster		=100/0	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: rs2059397; hg19: chr1-217718132;