9-137065662-G-A

Variant names:

• chr9-137065662-G-A
• rs371106227
• NM_178448.4:c.691C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178448.4(SAPCD2):​c.691C>T​(p.Gln231*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAPCD2 NM_178448.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

SAPCD2 (HGNC:28055): (suppressor APC domain containing 2) Involved in negative regulation of protein localization to cell cortex and positive regulation of cell population proliferation. Located in several cellular components, including apical cortex; apical junction complex; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178448.4. 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
	SAPCD2	NM_178448.4	MANE Select	c.691C>T	p.Gln231*	stop_gained	Exon 3 of 6	NP_848543.2	Q86UD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAPCD2	ENST00000409687.5	TSL:1 MANE Select	c.691C>T	p.Gln231*	stop_gained	Exon 3 of 6	ENSP00000386348.3	Q86UD0
	SAPCD2	ENST00000879034.1		c.781C>T	p.Gln261*	stop_gained	Exon 4 of 7	ENSP00000549093.1
	SAPCD2	ENST00000940023.1		c.781C>T	p.Gln261*	stop_gained	Exon 4 of 6	ENSP00000610082.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450356 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 719674

African (AFR) AF: 0.00 AC: 0 AN: 33212

American (AMR) AF: 0.00 AC: 0 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.00 AC: 0 AN: 39358

South Asian (SAS) AF: 0.00 AC: 0 AN: 85634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104224

Other (OTH) AF: 0.00 AC: 0 AN: 59894

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		3.6
Vest4		0.11
GERP RS		4.1
Mutation Taster		=41/159	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs371106227; hg19: chr9-139960114;