rs185066621

Variant names:

• chr1-2479840-C-T
• rs185066621
• NM_014638.4:c.378C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2479840-C-T
• chr1-2479840-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014638.4(PLCH2):​c.378C>T​(p.His126His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,609,320 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (5 hom.)
• Consequence: PLCH2 NM_014638.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.52
• Publications: 2 publications found

Genes affected

PLCH2 (HGNC:29037): (phospholipase C eta 2) PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-2479840-C-T is Benign according to our data. Variant chr1-2479840-C-T is described in ClinVar as Benign. ClinVar VariationId is 720201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014638.4. 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
	PLCH2	NM_014638.4	MANE Select	c.378C>T	p.His126His	synonymous	Exon 3 of 22	NP_055453.2
	PLCH2	NM_001303012.2		c.297C>T	p.His99His	synonymous	Exon 3 of 22	NP_001289941.1	O75038-2
	PLCH2	NM_001303013.1		c.438C>T	p.His146His	synonymous	Exon 3 of 22	NP_001289942.1	O75038

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH2	ENST00000378486.8	TSL:1 MANE Select	c.378C>T	p.His126His	synonymous	Exon 3 of 22	ENSP00000367747.3	O75038-1
	PLCH2	ENST00000419816.6	TSL:5	c.378C>T	p.His126His	synonymous	Exon 3 of 22	ENSP00000389803.2	O75038-1
	PLCH2	ENST00000449969.5	TSL:5	c.297C>T	p.His99His	synonymous	Exon 3 of 22	ENSP00000397289.1	O75038-2

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 527 AN: 152192 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000938 AC: 219 AN: 233386 AF XY: 0.000760

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000535

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000914

Gnomad FIN exome AF: 0.0000962

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.000526

GnomAD4 exome AF: 0.000402 AC: 585 AN: 1457010 Hom.: 5 Cov.: 30 AF XY: 0.000346 AC XY: 251 AN XY: 724730

African (AFR) AF: 0.0126 AC: 422 AN: 33404

American (AMR) AF: 0.000678 AC: 30 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.000354 AC: 14 AN: 39544

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85860

European-Finnish (FIN) AF: 0.0000777 AC: 4 AN: 51496

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5746

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1110584

Other (OTH) AF: 0.000848 AC: 51 AN: 60120

GnomAD4 genome AF: 0.00346 AC: 527 AN: 152310 Hom.: 2 Cov.: 33 AF XY: 0.00346 AC XY: 258 AN XY: 74474

African (AFR) AF: 0.0119 AC: 493 AN: 41546

American (AMR) AF: 0.00157 AC: 24 AN: 15308

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

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.00414

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-2.5
PromoterAI		0.028	Neutral
Mutation Taster		=99/1	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: rs185066621; hg19: chr1-2411279;