chr2-126693955-C-G

Variant names:

• chr2-126693955-C-G
• rs28387219
• NM_002101.5:c.190+8C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002101.5(GYPC):​c.190+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,582,978 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (59 hom.)
• Consequence: GYPC NM_002101.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001007
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.877
• Publications: 0 publications found

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GYPC Gene-Disease associations (from GenCC):

• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-126693955-C-G is Benign according to our data. Variant chr2-126693955-C-G is described in ClinVar as Benign. ClinVar VariationId is 779867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002101.5. 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
	GYPC	NM_002101.5	MANE Select	c.190+8C>G		splice_region intron	N/A	NP_002092.1	P04921-1
	GYPC	NM_016815.4		c.133+8C>G		splice_region intron	N/A	NP_058131.1	P04921-3
	GYPC	NM_001256584.2		c.127+8C>G		splice_region intron	N/A	NP_001243513.1	P04921-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	ENST00000259254.9	TSL:1 MANE Select	c.190+8C>G		splice_region intron	N/A	ENSP00000259254.4	P04921-1
	GYPC	ENST00000409836.3	TSL:1	c.133+8C>G		splice_region intron	N/A	ENSP00000386904.3	P04921-3
	GYPC	ENST00000356887.12	TSL:1	c.127+8C>G		splice_region intron	N/A	ENSP00000349354.7	P04921-2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2284 AN: 152086 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00512

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00403 AC: 1013 AN: 251234 AF XY: 0.00305

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00163 AC: 2335 AN: 1430774 Hom.: 59 Cov.: 27 AF XY: 0.00147 AC XY: 1050 AN XY: 713670

African (AFR) AF: 0.0537 AC: 1763 AN: 32832

American (AMR) AF: 0.00266 AC: 119 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39568

South Asian (SAS) AF: 0.000630 AC: 54 AN: 85652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00526 AC: 30 AN: 5706

European-Non Finnish (NFE) AF: 0.000115 AC: 125 AN: 1083596

Other (OTH) AF: 0.00404 AC: 240 AN: 59400

GnomAD4 genome AF: 0.0150 AC: 2290 AN: 152204 Hom.: 60 Cov.: 32 AF XY: 0.0154 AC XY: 1145 AN XY: 74418

African (AFR) AF: 0.0520 AC: 2160 AN: 41540

American (AMR) AF: 0.00511 AC: 78 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68016

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00433 Hom.: 2

Bravo AF: 0.0172

Asia WGS AF: 0.00578 AC: 21 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	GYPC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.38
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000010
dbscSNV1_RF	Benign	0.0
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: rs28387219; hg19: chr2-127451531;